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This study sought to identify potential pharmacogenetic associations of selected enzymes and transporters with type 2 diabetes (T2D). In addition, pharmacogenomic profiles, concentrations of asymmetric dimethylarginine (ADMA) or kidney injury molecule-1 (KIM-1), and several covariates were investigated. Whole blood was collected from 63 patients, with 32 individuals with T2D. A pharmacogenomic panel was used to assay genetic profiles, and biomarker ELISAs were run to determine subject concentrations of ADMA and KIM-1. Additive genetic modeling with multiple linear and logistic regressions were performed to discover potential SNPs-outcome associations using PLINK. Ten SNPs were found to be significant (p<0.05) depending on the inclusion or exclusion of covariates. Of these, four were found in association with the presence of T2D, rs2231142, rs1801280, rs1799929, and rs1801265 depending on covariate inclusion or exclusion. Regarding ADMA, one SNP was found to be significant without covariates, rs1048943. Five SNPs were identified in association with KIM-1 and T2D in the presence of covariates, rs12208357, rs34059508, rs1058930, rs1902023, and rs3745274. Biomarker concentrations were not significantly different in the presence of T2D. This exploratory study found several SNPs related to T2D; further research is required to validate and understand these relationships. [ABSTRACT FROM AUTHOR]

Abstract: HIV antiretroviral therapy spans several different drug classes, meant to combat various aspects of viral infection and replication. Many authors have argued the benefits of therapeutic drug monitoring (TDM) for the HIV patient including compliance assurance and assessment of appropriate drug concentrations; however, the array of drug chemistries and combinations makes TDM an arduous task. HPLC‐UV and LC‐MS/MS are both frequent instruments for the quantification of HIV drugs in biological matrices with investigators striving to balance sensitivity and affordability. Plasma, the dominant matrix for these analyses, is prepared using protein precipitation, liquid–liquid extraction or solid‐phase extraction depending on the specific complement of analytes. Despite the range of polarities found in drug classes relevant to HIV therapeutics, most chromatographic separations utilize a hydrophobic column (C18). Additionally, as the clinically relevant samples for these assays are infected with HIV, along with possible co‐infections, another important aspect of sample preparation concerns viral inactivation. Although not routine in clinical practice, many published analytical methods from the previous two decades have demonstrated the ability to conduct TDM in HIV patients receiving various medicinal combinations. This review summarizes the analytical methods relevant to TDM of HIV drugs, while highlighting respective challenges. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to non-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 µg/kg misoprostol). From day 3 to day 9, one celecoxib dose (40 mg/kg) replaced a vehicle dose of one group and one group received celecoxib in addition to misoprostol. Livers were harvested on day 10. No hepatic abnormalities were observed denoting a lack of influence by either drug. Also no change in mean biomarker levels was detected. The changes in hepatic celecoxib concentration in the misoprostol-receiving group compared to control were not significant. Thus misoprostol does not influence hepatic celecoxib effects in terms of histopathology, oxidative stress, or celecoxib concentration level at the dosage and duration examined. [ABSTRACT FROM AUTHOR]

Niacin is a highly effective, lipid regulating drug associated with a number of metabolically induced side effects such as prostaglandin (PG) mediated flushing and hepatic toxicity. In an attempt to reduce the development of these adverse effects, scientists have investigated differing methods of niacin delivery designed to control drug release and alter metabolism. However, despite successful formulation of various orally based capsule and tablet delivery systems, patient adherence to niacin therapy is still compromised by adverse events such as PG-induced flushing. While the primary advantage of orally dosed formulations is ease of use, alternative delivery options such as transdermal delivery or polymeric micro/nanoparticle encapsulation for oral administration have shown promise in niacin reformulation. However, the effectiveness of these alternative delivery options in reducing inimical effects of niacin and maintaining drug efficacy is still largely unknown and requires more in-depth investigation. In this paper, we present an overview of niacin applications, its metabolic pathways, and current drug delivery formulations. Focus is placed on oral immediate, sustained, and extended release niacin delivery as well as combined statin and/or prostaglandin antagonist niacin formulation. We also examine and discuss current findings involving transdermal niacin formulations and polymeric micro/nanoparticle encapsulated niacin delivery. [ABSTRACT FROM AUTHOR]

Nonsteroidal anti-inflammatory drugs (NSAIDs) can produce adverse effects by inhibiting prostaglandin (PG) synthesis. A PGE1 analogue, misoprostol, is often utilized to alleviate NSAID-related gastrointestinal side effects. This study examined the effect of misoprostol on celecoxib renal toxicity. Additionally, the effects of these drugs on cardiovascular parameters were evaluated. Four randomized rat groups were orally gavaged for 9 days, two groups receiving vehicle and two groups receiving misoprostol (100 µg/kg) twice daily. Celecoxib (40 mg/kg) was co-administered once daily to one vehicle and one misoprostol group from days 3 to 9. Urine and blood samples were collected and blood pressure parameters were measured during the study period. Hearts and kidneys were harvested on final day. Day 2 urinary electrolyte samples revealed significant reductions in sodium excretion in misoprostol (0.12±0.05 µmol/min/100 g) and misoprostol+celecoxib groups (0.07±0.02 µmol/min/100 g). At day 3, all treatment groups showed significantly reduced sodium excretion. Potassium excretion diminished significantly in vehicle+celecoxib and misoprostol+celecoxib groups from day 3 onward. Urinary kidney injury molecule-1 levels were significantly increased in vehicle+celecoxib (0.65±0.02 vs. 0.35±0.07 ng/mL, p = 0.0002) and misoprostol+celecoxib (0.61±0.06 vs. 0.37±0.06 ng/mL, p = 0.0015) groups when compared to baseline; while plasma levels of cardiac troponin I increased significantly in vehicle+celecoxib (p = 0.0040) and misoprostol+misoprostol (p = 0.0078) groups when compared to vehicle+vehicle. Blood pressure parameters increased significantly in all misoprostol treated groups. Significant elevation in diastolic (p = 0.0071) and mean blood pressure (p = 0.0153) was noted in misoprostol+celecoxib compared to vehicle+celecoxib. All treatments produced significant tubular dilatation/necrosis compared to control. No significant myocardial changes were noticed; however, three animals presented with pericarditis. Kidney, heart, and plasma celecoxib levels revealed no significant change between vehicle+celecoxib and misoprostol+celecoxib. Concomitant misoprostol administration did not prevent celecoxib renal toxicity, and instead exacerbated renal side effects. Misoprostol did not alter plasma or tissue celecoxib concentrations suggesting no pharmacokinetic interaction between celecoxib and misoprostol. [ABSTRACT FROM AUTHOR]