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ABSTRACT: Connections between the 2 scientific fields of physiology and dairy science have existed for a very long time—since the 19th century. One possible explanation for this circumstance could have been the necessity for financial support, which might have played a significant role for many theoretical physiologists to conduct studies on dairy products. This study discusses a correspondence written by the physiologist R. Gscheidlen to J. A. Winter, the main editor of the German (previously Saxon) journal “Schmidt's Yearbooks on the Entire Field of Domestic and Foreign Medicine” (“Schmids Jahrbücher der in–und ausländischen gesammten Medicin”). Gscheidlen submitted a review manuscript on the composition of milk to Winter's journal. In that work, which was published later as the first issue's very first article of the first volume (of in total 4 quarterly volumes) in 1871, Gscheidlen mainly refers to Eduard Kemmerich, who later became a pioneer of cattle breeding in Argentine. Therefore, studies on dairy products and on dairy science, although regularly not very significant from a theoretical and physiological point of view, obviously had concrete implications for practical purposes. Furthermore, other parts of Winter's journal, volume 1871, indicate that Gscheidlen tried to connect these studies with his early theoretical works on physiological metabolism. These theoretical studies included experiments that already explored basic principles of the urea cycle from today's point of view. Of course, these works, which were partly carried out on animals, must have been extravagant and expensive. For that reason, it is possible to assume that early dairy science and other scientific fields in Germany around 1870, which were linked to the developing food industry, had a very significant influence on the advances in theoretical metabolism physiology.

World War I not only resulted in a total of far more than 16,000,000 dead soldiers and civilians but also left countless soldiers with severe wounds and impairments. The present article focuses on the medical assessments of wounded soldiers during and after World War I. As many official files, including medical records of German World War I soldiers, were destroyed during World War II in April 1945, finding original materials on this topic is challenging. The following article examines an original correspondence between the surgeon, Georg Benno Schmidt (1860 – 1935), and the ophthalmologist, August Wagenmann (1863 – 1955), who were both full professors at Heidelberg University, which took place approximately 15 months after the end of World War I in 1919. This correspondence demonstrates the immense workload faced by physicians responsible for assessing World War I veterans, even more than a year after the war had ended.

The Austrian surgeon Erwin Payr can be regarded as an extraordinarily influential scholar and physician, both for the development of surgical science and clinical medicine around the time of World War I. Today the “Payr’s sign” and the “Payr’s disease” in clinical medicine are closely associated with Erwin Payr’s name and surgical instruments, like the “Payr pylorus clamp”, were also named after him. Furthermore, some of Erwin Payr’s former assistants and senior physicians, for example, Martin Kirschner (1879-1942), Herbert Olivecrona (1891-1980), Antoni Tomasz Jurasz (1882-1961), Masao Sumita (1878-1946), Otto Kleinschmidt (1880-1948), Josef Hohlbaum (1884-1945), Paul Frangenheim (1876-1930), Heinrich Kuntzen (1893-1977), and Ernst Heller (1877-1964), in part later became extremely influential surgeons and international medical scholars. This article discusses an original historical correspondence from Payr to Emil Krückmann (1865-1944) from October 7, 1916. This original correspondence also includes a handwritten message to Arthur Brückner (1877-1975), written by an unidentifiable physician on the backside of the typewritten correspondence. The existence of this original material shows that surgery in World War I partly had a very provisional character and that the treatment of the patients could have been, at least to some extent, chaotic and not well organized with frequent changes in the physicians’ responsibility for their patients.

Introduction The early geneticist and psychiatrist Ernst Rüdin (1874–1952) became one of the key figures in the eugenics movement and in the German health system of the Nazi era. His connections in the international eugenics network have played an important role in the history of eugenics.

The surgeon Anton von Eiselsberg can be regarded as one of Austria’s most influential physicians. This article presents historical materials in connection with Eiselsberg, including a letter from him sent on October 17, 1914, when World War I had already begun and the first wounded soldiers had to be treated in the field hospitals. Therefore, I focus on Eiselsberg’s role as an admiral staff physician in the Austrian Navy between 1914 and 1918. Eiselsberg’s treatment (1915 – 1917) of King Constantine I from Greece and Eiselsberg’s visit to the Osman Empire in 1918 are especially interesting and can be regarded as notable aspects of World War I history of medicine in the Middle East. In his autobiography, written in 1937, Anton von Eiselsberg clearly wrote that shots in the abdomen often could not be treated properly in World War I due to the lack of surgical capacities.Furthermore, I present biographical data of Eiselsberg’s life. The Eiselsberg family was part of Austria’s landed gentry. Anton von Eiselsberg attended a Christian Catholic monastery school as a child. This might be one of the reasons why his political positions later were often close to religious Catholic Christian conservativism.

This study focuses on a correspondence between the surgeon, Fedor Krause (1857 – 1937), and the neurologist, Arthur Simons (1877 – 1942), who specialized in muscle neurology. The correspondence shows many interesting aspects of surgery at the time of World War I. It is especially remarkable that the important surgeon, August Bier (1861 – 1949), is criticized in this correspondence. One major problem of German surgery at the beginning of the 20th century was the fact that patients often were not mobilized sufficiently and instead, unnecessarily were told to stay in bed (“Bettruhe”) for many weeks, and in many cases, patients also were unnecessarily told to move as little as possible. Even giving massages was considered harmful. This is in contrast to today’s principle of early mobility (ERAS). The correspondence between these two scholars clearly indicates that these wrong principles were propagated by certain important surgeons in Germany (like August Bier) and that these principles were rather based on their personal opinions than on scientific evidence. More than 100 years ago, there were already some physicians, like Arthur Simons or Fedor Krause, who openly criticized these wrong approaches in German surgery.

Background: The current literature highlights a strong link between the poor health outcomes of transgender and gender diverse (TGD) individuals and their negative experiences in various areas of life. Most of these publications rely on adults' memories, lacking a focus on the current experiences and needs of young transgender and gender-diverse individuals. Furthermore, previous studies on support for these young people often solely consider the perspectives of TGD adults or professionals and rarely involve parents' viewpoints., Methods: This study will use a mixed sequential method with a participatory approach. Firstly, the qualitative phase will explore the difficulties and needs of TGD (15-20 years old) and of the families and professionals who support them. Results from this part will be used to develop the questionnaire for the quantitative phase, with the help of a community board. Secondly, based on participatory epidemiological research, the quantitative phase will use an intersectional perspective to measure the impact of individual and structural factors on the quality of life and well-being of transgender and gender-diverse young people. Finally, a co-creation phase will be undertaken to formulate recommendations based on the results of the first two phases., Discussion: This research aims at better understanding the influence of gender identity on the quality of life and health of TGD young people and their families and to identify protective and risk factors that affect their vulnerabilities., Ethics and Dissemination: This study has been approved by the Ethics Committee of the Erasme Faculty Hospital (CCB B4062023000140). As this research is participatory and part of a PhD dissertation, we aim to disseminate the results through our partners' networks and structures locally, and internationally through conferences and peer-reviewed journals., (© 2024. The Author(s).)

Objective: To describe step-by-step surgical techniques and report outcomes of the largest single-centre series of patients with distal ureteric disease exclusively treated with robot-assisted ureteric reimplantation with Boari flap (RABFUR) and psoas hitch (RAPHUR), with a minimum follow-up of 1 year and complete postoperative data., Patients and Methods: A total of 37 patients with distal ureteric disease were treated between 2010 and 2018. Of these, 81% and 19% underwent RAPHUR and RABFUR, respectively. Intra-, peri- and postoperative outcomes were assessed. The 90-day postoperative complications were reported according to the standardised methodology proposed by the European Association of Urology Ad Hoc Panel. Functional outcomes (creatinine, estimated glomerular filtration rate [eGFR]) and postoperative symptoms (visual analogue pain scale) were assessed., Results: The median operating time and blood loss were 180 min and 100 mL, respectively. There were no conversions to open surgery and no intraoperative transfusions. The median length of stay, bladder catheter indwelling time and stent removal were 4, 7 and 30 days, respectively. The median follow-up was 24 months. Overall, 10 patients (27%) had postoperative complications and of these, eight (22%) and two (5.4%) were Clavien-Dindo Grade I-II and III, respectively. At the last follow-up, the median postoperative creatinine level and eGFR were 0.9 mg/dL and 73.5 mL/min/1.73 m 2 , respectively. At the last follow-up, five (13.5%) and three (8%) patients had Grade 1 hydronephrosis and mild urinary symptoms, respectively. The study limitations include its retrospective nature., Conclusion: In the present study, we present our RABFUR and RAPHUR techniques. We confirm the feasibility and safety profile of both approaches in patients with distal ureteric disease relying on the largest single-centre series with ≥1 year of follow-up., (© 2021 The AuthorsBJU International © 2021 BJU International.)

Background: The feasibility and efficacy of robot-assisted radical prostatectomy (RARP) in locally advanced prostate cancer (PCa) patients with iT3 lesion at magnetic resonance imaging (MRI) are currently not explored., Objective: To describe our revised RARP technique (ie, superextended RARP [SE-RARP]) for PCa patients with posterior iT3a or iT3b at MRI., Design, Setting, and Participants: Data from 89 patients with posterior iT3a or T3b disease who underwent SE-RARP at a single high-volume centre between 2015 and 2018 were analysed., Surgical Procedure: RARP was performed using a DaVinci Xi system. The surgical approach provided an inter- or extrafascial RARP where Denonvilliers' fascia and perirectal fat were dissected free and left on the posterior surface of the seminal vesicles., Measurements: Perioperative outcomes, and intra- and postoperative complications were assessed. Postoperative outcomes were assessed in patients with complete follow-up data (n = 78). Biochemical recurrence (BCR) was defined as two consecutive prostate-specific antigen values of ≥0.2 ng/ml. Urinary continence (UC) recovery was defined as the use of zero or one safety pad. Kaplan-Meier and multivariable Cox regression models were used., Results and Limitations: The median operative time, blood loss, and length of stay were 204 min, 300 ml, and 5 d, respectively. The median bladder catheterisation time was 5 d. Overall, 28%, 28%, and 27% of patients had pathological grade group (GG) 4-5, pT3b, and positive surgical margins (PSMs), respectively. Three patients (3.4%) experienced intraoperative complications. Among patients with available follow-up data (n = 78), 14 (18%) experienced 30-d postoperative complications. The median follow-up was 19 mo. Overall, 11 patients received additional treatment. At 2 yr of follow-up, BCR-free and additional treatment-free survival were 55% and 66%, respectively. Pathological GG 4-5 (hazard ratio [HR] 3.2) and PSM (HR 5.8) were independent predictors of recurrence, as well as of additional treatment use (HR 5.6 for GG 4-5 and 5.2 for PSM). The 1-yr UC recovery was 84%., Conclusions: We presented our revised RARP technique applicable to patients with posterior iT3a or iT3b at preoperative MRI. This technique is associated with good morbidity and continence recovery rates, and might guarantee biochemical control of the disease and postpone the use of additional treatments in patients with low-grade and negative surgical margins., Patient Summary: A revised robot-assisted radical prostatectomy technique applicable to prostate cancer patients with posterior iT3a or iT3b lesion at magnetic resonance imaging was described. This novel technique is feasible and safe in expert hands., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: The available studies comparing robot-assisted radical cystectomy (RARC) with intracorporeal (ICUD) vs. extracorporeal (ECUD) urinary diversion have not relied on a standardized methodology to report complications and did not assess the effect of different approaches on postoperative outcomes., Materials: Two hundred and sixty seven patients treated with RARC at a single center were assessed. A retrospective analysis of data prospectively collected according to a standardized methodology was performed. Multivariable logistic regression models (MVA) assessed the impact of ICUD vs. ECUD on intraoperative complications, prolonged length of stay (LOS), 30-day Clavien Dindo (CD) ≥ 2 complications and readmission rate. Interaction terms tested the impact of the approach on different patient subgroups. Lowess graphically depicted the probability of CD ≥ 2 after ICUD or ECUD according to patient baseline characteristics., Results: Overall, 162 ICUD vs 105 ECUD (61 vs. 39%) were performed. Intraoperative complications were recorded in 24 patients. The median LOS and readmission rate were 11 vs. 13 (p = 0.02) and 24 vs. 22% (p = 0.7) in ICUD vs. ECUD, respectively. Overall, 227 postoperative complications were recorded. The overall rate of CD ≥ 2 was 35 and 43% in patients with ICUD vs. ECUD, respectively (p = 0.2). At MVA, the approach type was not an independent predictor of any postoperative outcomes (all p ≥ 0.4). Age-adjusted Charlson Comorbidity Index (ACCI) was associated with an increased risk of CD ≥ 2 (OR: 1.2, p = 0.006). We identified a significant interaction term between ACCI and approach type (p = 0.04), where patients with ICUD had lower risk of CD ≥ 2 relative to those with ECUD with increasing ACCI., Conclusions: Relying on a standardized methodology to report complications, we observed that highly comorbid patients who undergo ICUD have lower risk of postoperative complications relative to those patients who received ECUD.

Purpose: The aim of the current narrative review was to summarize the available evidence in the literature on artificial intelligence (AI) methods that have been applied during robotic surgery., Methods: A narrative review of the literature was performed on MEDLINE/Pubmed and Scopus database on the topics of artificial intelligence, autonomous surgery, machine learning, robotic surgery, and surgical navigation, focusing on articles published between January 2015 and June 2019. All available evidences were analyzed and summarized herein after an interactive peer-review process of the panel., Literature Review: The preliminary results of the implementation of AI in clinical setting are encouraging. By providing a readout of the full telemetry and a sophisticated viewing console, robot-assisted surgery can be used to study and refine the application of AI in surgical practice. Machine learning approaches strengthen the feedback regarding surgical skills acquisition, efficiency of the surgical process, surgical guidance and prediction of postoperative outcomes. Tension-sensors on the robotic arms and the integration of augmented reality methods can help enhance the surgical experience and monitor organ movements., Conclusions: The use of AI in robotic surgery is expected to have a significant impact on future surgical training as well as enhance the surgical experience during a procedure. Both aim to realize precision surgery and thus to increase the quality of the surgical care. Implementation of AI in master-slave robotic surgery may allow for the careful, step-by-step consideration of autonomous robotic surgery.

Vitamin K (VK) is a fat-soluble vitamin that vertebrates have to acquire from the diet, since they are not able to de novo synthesize it. VK has been historically known to be required for the control of blood coagulation, and more recently, bone development and homeostasis. Our understanding of the VK metabolism and the VK-related molecular pathways has been also increased, and the two main VK-related pathways-the pregnane X receptor (PXR) transactivation and the co-factor role on the γ-glutamyl carboxylation of the VK dependent proteins-have been thoroughly investigated during the last decades. Although several studies evidenced how VK may have a broader VK biological function than previously thought, including the reproduction, little is known about the specific molecular pathways. In vertebrates, sex differentiation and gametogenesis are tightly regulated processes through a highly complex molecular, cellular and tissue crosstalk. Here, VK metabolism and related pathways, as well as how gametogenesis might be impacted by VK nutritional status, will be reviewed. Critical knowledge gaps and future perspectives on how the different VK-related pathways come into play on vertebrate's reproduction will be identified and proposed. The present review will pave the research progress to warrant a successful reproductive status through VK nutritional interventions as well as towards the establishment of reliable biomarkers for determining proper nutritional VK status in vertebrates.

Bisphenol A (BPA), a monomer used for polycarbonate manufacture, has been widely reported as an endocrine-disrupting chemical (EDC). Among other alterations, BPA induces reproductive dysfunctionalities. Changes in the endocannabinoid system (ECS) have been recently shown to be associated with reproductive disorders. The ECS is a lipid-based signaling system (cannabinoid receptors, endocannabinoids and enzymatic machinery) involved in several physiological functions. The main goal of the present study was to assess the effects of two environmental concentrations of BPA (10 and 20 μg/L) on the ECS in 1-year old zebrafish gonads. In males, BPA increased the gonadosomatic index (GSI) and altered testicular levels of endocannabinoids as well as reduced the testicular area occupied by spermatogonia. In male liver, exposure to 20 μg/L BPA significantly increased vitellogenin (vtg) transcript levels. In female zebrafish, BPA altered ovarian endocannabinoid levels, elevated hepatic vtg mRNA levels as well as increased the percentage of vitellogenic oocytes in the ovaries. In conclusion, exposure to two environmentally relevant concentrations of BPA altered the ECS and consequently, gonadal function in both male and female zebrafish., Competing Interests: Declaration of competing interest None., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

This paper summarizes efforts to (i) better understand the behavior of amorphous solid dispersions (ASDs) under real-life dosing conditions and (ii) evaluate the capability of in vitro methodologies to capture gastro-intestinal drug disposition. In a first part of the study, five healthy volunteers participated in a two-way crossover trial in which one Norvir® tablet (100 mg ritonavir) was dosed under fasted and fasted + PPI conditions. Gastrointestinal aspirates were collected from both the stomach and duodenum as a function of time to map the gastrointestinal drug disposition of the ritonavir ASD formulation and to evaluate the impact of reduced gastric acid secretion on formulation performance. In both test conditions, ritonavir was shown to supersaturate in the upper GI tract illustrating the capacity of the formulation strategy itself to generate supersaturated drug content. In parallel, in vivo test conditions were closely mimicked in a multitude of in vitro methodologies (i.e., USP II dissolution apparatus, BioGIT and TIM-1 system) with the aim to evaluate their ability to predict in vivo gastrointestinal drug disposition. The selected in vitro methodologies were found capable of qualitatively and/or quantitatively picking up trends observed in the intraluminal sampling study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Vitamin K (VK) is a key nutrient for several biological processes (e.g., blood clotting and bone metabolism). To fulfill VK nutritional requirements, VK action as an activator of pregnane X receptor (Pxr) signaling pathway, and as a co-factor of γ-glutamyl carboxylase enzyme, should be considered. In this regard, VK recycling through vitamin K epoxide reductases (Vkors) is essential and should be better understood. Here, the expression patterns of vitamin K epoxide reductase complex subunit 1 ( vkorc1 ) and vkorc1 like 1 ( vkorc1l1 ) were determined during the larval ontogeny of Senegalese sole ( Solea senegalensis ), and in early juveniles cultured under different physiological conditions. Full-length transcripts for ssvkorc1 and ssvkorc1l1 were determined and peptide sequences were found to be evolutionarily conserved. During larval development, expression of ssvkorc1 showed a slight increase during absence or low feed intake. Expression of ssvkorc1l1 continuously decreased until 24 h post-fertilization, and remained constant afterwards. Both ssvkors were ubiquitously expressed in adult tissues, and highest expression was found in liver for ssvkorc1 , and ovary and brain for ssvkorc1l1 . Expression of ssvkorc1 and ssvkorc1l1 was differentially regulated under physiological conditions related to fasting and re-feeding, but also under VK dietary supplementation and induced deficiency. The present work provides new and basic molecular clues evidencing how VK metabolism in marine fish is sensitive to nutritional and environmental conditions.

Objective: To describe the initial experiencein our center on targeted prostate biopsies (TB) using Magnetic Resonance imaging/ultrasonography (MRI/US) fusion and to compare PCa detection with systematic biopsies (SB)., Patients and Me Thods: A retrospective, descriptive and comparative study was conducted on the first 94 men who underwent TB using MRU/US fusion in our center since February 2017 to March 2018. All patients underwent a protocol of 6-12 cores of systematic biopsies (SB) (except 9) and 2-6 targeted coreson the MRI index lesion. The Hitachi/HiVision Preirus equipment was used with RVS software (Real-time virtual sonography) and a biplane transducer for the fusion imaging procedure. Clinically significant PCa (csPCa) was defined as: at least one core with a Gleason score of 3+4., Results: The proportion of patients diagnosed with PCa was higher in TB compared with SB (p=0.035) and the mean of core performed for diagnosis was lower in TB compared with SB (p<0.001). A trend towards an improved detection of csPCa in TB compared to SB was observed (p=0.063)., Conclusions: The MRI/US fusion targeted biopsies (TB) showed a higher detection rate of PCa, with less cores taken for diagnosis and a tendency to better identification of csCaP compared to SB.

Following a previous study which aimed to determine the interlaboratory reproducibility of biorelevant dissolution testing in the USP 2 apparatus for commercial formulations of two weak acids (ibuprofen and zafirlukast), this study attempts to determine the interlaboratory reproducibility using a similar protocol for a commercially available formulation of a weak base, indinavir. Fourteen partners including twelve industrial and two academic partners participated in this study. To ensure uniformity, all partners were provided with a standardized protocol to perform (i) a single medium dissolution test in fasted state simulated gastric and intestinal fluids (FaSSGF and FaSSIF, respectively) and (ii) a two-stage dissolution experiment simulating gastrointestinal transfer. Optionally, partners could run a single-stage dissolution test in fed state simulated intestinal fluid (FeSSIF). For each dissolution test, one Crixivan® capsule (containing 400 mg indinavir as its sulfate salt) was added as dose of interest. For the single medium dissolution test in FaSSIF, all partners observed rapid release of indinavir resulting in supersaturated concentrations, followed by precipitation to equilibrium solubility. The degree and period of supersaturation varied among the participating laboratories. Average dissolution profiles in FeSSIF appeared to be highly reproducible with dissolved concentrations remaining lower than the thermodynamic solubility of indinavir in FeSSIF. For the two-stage dissolution test, most partners observed supersaturated concentrations in the intestinal compartment; two partners observed no supersaturation due to immediate precipitation. Given the fact that a high interlaboratory but low intralaboratory variability was observed when supersaturation/precipitation occurred, an undefined factor was hypothesized as a potential cause of the variability in precipitation. Hence, the impact of several experimental factors on the supersaturation and precipitation behavior of indinavir was investigated in a next step. The investigation indicated that variability is likely attributable to a combination of factors, especially, the time elapsed between sampling and dilution of the sample with the mobile phase. Therefore, when designing a test in which supersaturation and precipitation is anticipated, stringent control of the test methodology, especially regarding sampling and dilution, is needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Advances in understanding of human disease have prompted the U.S. Food and Drug Administration to classify certain molecules as "break-through therapies," providing an accelerated review that may potentially enhance the quality of patient lives. With this designation come compressed timelines to develop drug products, which are not only suitable for clinic trials but can also be approved and brought to the market rapidly. Early risk identification for decreased oral absorption due to drug-drug interactions with proton pump inhibitors (PPIs) or acid-reducing agents (ARAs) is paramount to an effective drug product development strategy. An early ARA/PPI drug-drug interaction (DDI) risk identification strategy has been developed using physiologically based absorption modeling that readily integrates ADMET predictor generated in silico estimates or measured in vitro solubility, permeability, and ionization constants. Observed or predicted pH-solubility profile data along with pKas and drug dosing parameters were used to calculate a fraction of drug absorbed ratio in absence and presence of ARAs/PPIs. An integrated physiologically based pharmacokinetic absorption model using GastroPlus™ with pKa values fitted to measured pH-solubility profile data along with measured permeability data correctly identified the observed ARA/PPI DDI for 78% (16/22) of the clinical studies. Formulation strategies for compounds with an anticipated pH-mediated DDI risk are presented., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to evaluate the usefulness of the in vitro biorelevant gastrointestinal transfer (BioGIT) system in assessing the impact of dose and formulation on early exposure by comparing in vitro data with previously collected human plasma data of low solubility active pharmaceutical ingredients. Eight model active pharmaceutical ingredients were tested; Lu 35-138C (salt of weak base in a HP-beta-CD solution, three doses), fenofibrate (solid dispersion, tablet, two doses), AZD2207 EQ (salt of weak base, capsule, three doses), posaconazole (Noxafil® suspension, two doses), SB705498 (weak base, tablets vs. capsules), cyclosporine A (Sandimmun® vs. Sandimmun® Neoral), nifedipine (Adalat® capsule vs. Macorel® tablet), and itraconazole (Sporanox® capsule vs. Sporanox® solution). AUC 0-0.75h values were calculated from the apparent concentration versus time data in the duodenal compartment of the BioGIT system. Differences in AUC 0-0.75h values were evaluated versus differences in AUC 0-1h and in AUC 0-2h values calculated from previously collected plasma data in healthy adults. Ratios of mean AUC 0-0.75h , mean AUC 0-1h , and mean AUC 0-2h values were estimated using the lowest dose or the formulation with the lower AUC 0-0.75h value as denominator. The BioGIT system qualitatively identified the impact of dose and of formulation on early exposure in all cases. Log-transformed mean BioGIT AUC 0-0.75h ratios correlated significantly with log-transformed mean plasma AUC 0-1h ratios. Based on this correlation, BioGIT AUC 0-0.75h ratios between 0.3 and 10 directly reflect corresponding plasma AUC 0-1h ratios. BioGIT system is a valuable tool for the assessment of the impact of dose and formulation on early exposure to low solubility drugs.