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Pharmacokinetic and clinical studies of ceftizoxime (CZX) in the perinatal period gave the following results: 1. Peak concentrations of CZX in the maternal serum, umbilical cord serum and amniotic fluid in mothers after one intravenous injection of 1 g were, respectively, 70.2 micrograms/ml at 0 hour; 15.7 micrograms/ml at 0.5 hour; and 10-30 micrograms/ml at 3-6 hours. Concentrations of CZX in the neonatal serum were 0.87-13.5 micrograms/ml during 6-14 hours after parturition. The mean concentration of CZX in the milk in 1-8 hours after injection was less than 0.32-0.52 microgram/ml. 2. Good or excellent clinical efficacy was obtained in 28 of the 29 patients with perinatal infections, with an efficacy rate of 96.6%. Prophylactic effectiveness was obtained in 14 of the 15 patients, with an efficacy rate of 93.3%. 3. No side effects were observed in 44 cases. GOT and GPT values increased slightly in 1 patient. No abnormal values in total serum bilirubin or other parameters were found in any neonates after parturition. 4. The above results suggest that CZX is safe and effective for the treatment and prophylaxis of infection in the perinatal period.

Acyclovir (ACV), an antiviral nucleoside analog, is active against Herpes simplex viruses (HSV1, HSV2) and varicella virus (VZV). These viruses seems to be prejudicial to the pregnant woman and to the fetus. Yet, ACV is not recommended for use in pregnancy. However in certain cases, this drug has been used. We review in this paper, the pharmacokinetics and transplacental passage of ACV, indications, and whether the benefits of the administration of ACV in pregnancy outweigh the theoretical risks. Peak and trough plasma concentrations of ACV in pregnant women seem to be lower as compared to those of non-pregnant adults but effective. This drug crosses the placenta. Levels of ACV in cord blood ranged from 0.5 to 3 mumol/l. In as much as in vitro inhibitory doses 50 (ID 50) for HSV1, HSV2 and VZV ranged from 0.1 to 3 mumol/l, it is quite likely that levels noted above may be effective for in utero inhibition of viral replication. No adverse effects were noted in newborn exposed in utero to ACV. But one must be careful about the direct effects of this drug on nucleic acid metabolism despite encouraging results on animal fetuses. Based on these findings and from our experience, ACV can be administered in pregnancy in two particular situations: in cases of maternal severe viral infections and in order to inhibit in utero VZV replication. Doses required for pregnant women range from 5 to 15 mg/kg/8 hours given intravenously, and 200 mg of oral Acyclovir 5 times daily.

We previously reported a study on the antimicrobial action of a chemically synthesized drug, ofloxacin (OFLX) and on its transfer in. This paper describes the results of our clinical study on OFLX. 1. Only small fractions of intra-blood OFLX were transported into female organs such as uterus, ovary and fallopian tube. Our study with the normal delivery method shows that umbilical cord blood concentrations of OFLX is a third to a sixth of maternal blood concentrations and is achieved through trans-placental transfer. Its transfer into amniotic fluid, however, is very low. 2. Forty-one cases, including cases of female intrapelvic inflammation, urinary tract infection, puerperal mastitis, etc., were administered with OFLX at levels of 200 approximately 400 mg/day for 3 approximately 10 days. OFLX were found to be effective in 35 cases. 3. We observed 113 cases to which OFLX was administered, and found only 4 cases of gastrointestinal disturbance and 1 case of suspicion of drug eruption as side effects. Laboratory tests showed no abnormalities due to OFLX in blood, serum biochemical or urine value in the cases examined (26 to 51 cases depending on test).

The pharmacokinetics of ampicillin was studied in 38 patients with acute pyelonephritis in the second and third trimesters of pregnancy after the first and the last (28th-32nd) intramuscular injections of the antibiotic. The ampicillin levels in the blood and urine were determined with the agar diffusion method. The pharmacokinetic parameters were estimated in a one-compartmental model by computer The ampicillin levels in the blood and urine of the patients did not practically differ at all the investigation periods (0.5-6 hours after the antibiotic administration) in the second and third trimesters of pregnancy. During the treatment, the rate of ampicillin elimination from the host increased and the period of half-elimination from the blood decreased. The antibiotic levels in the urine within 4-6 hours after the last injection were practically lower in the second trimester of pregnancy as compared with the second trimester. The therapy resulted in an increase in the antibiotic renal clearance, which returned to normal in the second trimester of pregnancy and remained under normal in the third trimester of pregnancy. The increase was due to an approximately 2-fold acceleration of the rate of ampicillin secretion by the renal tubules. The total clearance of ampicillin practically increased in the second trimester of pregnancy and remained decreased in the third trimester of pregnancy. The estimation performed in accordance with the Krueger-Timmer principles on the basis of the characteristic features of the pharmacokinetics of ampicillin shown in the study provides recommendation of the following scheme for pyelonephritis treatment in pregnant women: 500 mg of ampicillin injected intramuscularly every 6 hours followed by gradual decreasing of the intervals between the injections to 4 hours as the rate of ampicillin elimination increases.

Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be representative for pregnancy as such. Marked changes in most organ systems, particularly in renal function, but in composition and amounts of body fluids as well, make it likely that several pharmacokinetic parameters change, possibly gradually as pregnancy progresses. Accumulated data for several beta-lactam antibiotics, and also for aminoglycosides indicate that antibiotics eliminated mainly by renal excretion will produce lower levels in serum or plasma in pregnant women than in other individuals. Also, the half-life of certain antibiotics in serum is shorter during pregnancy. Transplacental passage occurs for all antibiotics according to the physicochemical properties of the drug. Bolus injections to a pregnant woman are more efficient than continuous infusion in producing high levels of antibiotic in fetal serum and amniotic fluid. Fetal tissue levels are higher following multiple doses than after a single dose. Lower serum levels of antibiotics in pregnant women than in other individuals following the same dosage will be unsatisfactory as micr-organisms are less likely to be affected.

Quinine dihydrochloride (10 mg or, in two patients, a loading dose of 20 mg kg-1) was infused intravenously over 4 h in ten severely ill but conscious women with falciparum malaria complicating the third trimester of pregnancy. Plasma quinine concentrations, measured spectrophotofluorimetrically after benzene extraction, fitted closely a single exponential decline after the intravenous infusion. These data were therefore fitted to a one compartment model: total apparent volume of distribution, V, 0.96 +/- 0.27 l kg-1 (+/- s.d.), elimination half-time (t1/2,z), 11.3 +/- 4.3 h, total clearance, 1.22 +/- 0.77 ml min-1 kg-1. There was no relationship between arterial blood pressure and plasma quinine concentrations. Eight women delivered of live infants while taking quinine, had placental cord plasma quinine concentrations from 1.0 to 4.6 mg l-1 (mean 2.4) which correlated significantly with maternal plasma quinine concentrations (r = 0.78, t = 3.06, P less than 0.05). The mean (+/- s.d.) ratio of cord plasma to maternal plasma quinine concentration was 0.32 +/- 0.14. Heart blood from a foetus aborted at term had a plasma quinine concentration of 2.8 mg l-1; simultaneous maternal plasma quinine was 7.1 mg l-1 (ratio 0.39). Breast milk quinine concentrations and milk to plasma ratios were 0.5-3.6 mg l-1 (mean 2.6) and 0.11-0.53 (mean 0.31) in twenty-five women who were breast-feeding and had taken oral quinine sulphate for 1-10 days (mean 4.0). Five women with more serious infections received intravenous quinine; breast milk quinine concentrations ranged between 0.5 and 8.0 mg l-1 (mean 3.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Ureaplasma urealyticum has been implicated in gynaecological, obstetrical and neonatal pathology. Increased levels of C-reactive protein and total IgM concentrations in cord blood have often been used as a screening method for infectious disease in the fetus and the newborn. Analysis of the isolation rate of U. urealyticum in function of the concentrations of these two parameters in cord blood showed that U. urealyticum was significantly (P less than 0.05) more frequently isolated when CRP was above normal in cord blood. No correlation between the IgM level in the newborn and the presence of U. urealyticum could be established. A significant relationship was found (P less than 0.01) between Ureaplasma isolation in the urine of mother and child on the one hand and gestational age on the other hand, which supports the hypothesis that U. urealyticum may play a role in preterm delivery.

Although prostaglandins (PGs) are considered the key mediators of human parturition at term, there is a paucity of data regarding their participation in the mechanisms responsible for preterm labor. The purpose of this study was to establish if preterm labor is associated with changes in the amniotic fluid concentrations of prostaglandins. PGF2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) and 11-deoxy-13,14-dihydro-15-keto-11,16-cyclo-prostaglandin E2 (PGEM-ll) were measured by using specific and sensitive radioimmunoassays. Amniotic fluid was retrieved by transabdominal amniocentesis from 55 women with preterm labor and intact membranes. Patients were divided into three groups according to the response to tocolysis and the presence or absence of an intra-amniotic infection. Amniotic fluid concentrations of PGFM and PGEM-ll were significantly greater in women with preterm labor and intra-amniotic infection than in women without infection. In addition, patients unresponsive to tocolysis without intra-amniotic infection also had a significantly greater concentration of PGFM and PGEM-ll in amniotic fluid than those responsive to tocolysis. Amniotic fluid concentrations of PGF2 alpha were greater in women with intra-amniotic infection than in women without intra-amniotic infection. In the absence of intra-amniotic infection, no difference in amniotic fluid PGF2 alpha concentrations could be found between women who responded to tocolytic treatment and those who did not.

We report a case of miliary tuberculosis in a pregnant Jamaican woman in whom foetal exposure to ethambutol has been assessed. The mother received 15 mg/kg ethambutol as part of her antituberculosis therapy. Immediately after delivery, amniotic fluid, maternal, placental, and cord blood specimens were obtained and analysed for ethambutol concentrations. The levels were within the therapeutic range in all 4 samples. The concentrations indicate that the placenta is not a significant physiological barrier to the transfer of ethambutol to the foetus.

The pharmacokinetics of cephradine, a cephalosporin with a low degree of protein binding, was studied in 12 women after oral and intravenous administration of the drug during and after pregnancy. Six of the 12 women also received a cephalosporin with a high degree of protein binding, cefazolin, intravenously during and after pregnancy. For both drugs most pharmacokinetic parameters were altered in pregnancy. The area under the plasma concentration-time curve (AUC) following intravenous administration was smaller for both drugs during as compared to after pregnancy (mean change 39% for cephradine and 31% for cefazolin). Half-lives of both drugs were significantly shorter during compared with after pregnancy (mean change 26% for cephradine and 35% for cefazolin). Consequently, total body clearance was increased during pregnancy. A significant negative correlation between length of gestation and total clearance per kg bodyweight was seen for cephradine. The bioavailability of oral cephradine did not differ significantly during compared with after pregnancy. It is concluded that the dosage of both cefazolin and cephradine should be increased when treating infections in pregnant women in order to obtain the same antibacterial effect as when treating non-pregnant women.

Cytotoxicity of peritoneal cells in a HSV-infected murine model is attenuated in late pregnancy. Prostacyclin (PGI2) is elevated at this time in reproductive tissues and has been implicated in the regulation of the immune response. The purpose of this study was to estimate PGI2 in the peritoneal wash or culture supernatants of peritoneal cells obtained from uninfected and HSV-infected pregnant and virgin mice using a radioimmunoassay for 6-keto-prostaglandin F1 alpha. The peritoneal wash of uninfected pregnant and virgin mice contained high levels of 6-keto-PGF1 alpha, 505 +/- 51 pg/100 microliters, (mean +/- S.E., n = 15), and 200 +/- 19 pg/100 microliters, (n = 30), ad did peritoneal effector and target cell cultures (1,159 +/- 118 pg/100 microliters, n = 6, and 1,057 +/- 207 pg/100 microliters, n = 7), respectively. HSV-infection induced in vitro cytotoxicity and suppressed the release of 6-keto-PGF 1 alpha (r = -0.897, P less than 0.05, n = 18). Its concentration was significantly higher (14-fold, P less than .05) in the peritoneal wash, but not in the cell culture, of pregnant (212 +/- 29 pg/100 microliters, n = 19) as compared to virgin mice (18.5 +/- 3.4 pg/100 microliters, n = 27). The levels of 6-keto-PGF1 alpha were inversely correlated (P less than .05) with the combined effects of HSV-infection and cytotoxicity.

Pharmacokinetic characteristics of metronidazole were studied in 19 pregnant women with Trichomoniasis urogenitalis who had been hospitalized for legal abortion. All patients received 250 mg or 1.0 g metronidazole (Vagimid) per os in a single or multiple dose. Peak levels were reached 1-2 h after application. Mean serum levels of metronidazole were somewhat lower in gravidae than those in nonpregnant women. The mean elimination half-life values were 5.7 and 7.7 h after intake of 250 mg and 1.0 g metronidazole, respectively. As suggested by our pharmacokinetic results, the dosage regimen for treatment of anaerobic bacteria infection or parasitic infection in pregnant women can be the same as in nonpregnant patients.

The efficacy, tolerance, and safety of cefotetan--a new 7-alpha-methoxy cephalosporin--was assessed in controlled and uncontrolled evaluations involving 131 evaluable patients hospitalized with obstetric and gynecologic infections. The 99% satisfactory clinical response rate obtained with this drug was equivalent to that obtained with either moxalactam or cefoxitin, yet the mean amount of cefotetan given was lower than that of the other two drugs. Cefotetan was well tolerated and produced no major adverse reactions. In this era of Diagnosis Related Groups and cost containment, the twice-daily dosage schedule of cefotetan is a decided cost benefit.

Examining serum level values and urinary concentrations taken from non-pregnant control persons and pregnant women suffering from urinary tract infections (UTI) during the III. trimenon, the pharmacokinetic dates after single and repeated applications of 4 g azlocillin have been evaluated. We used a computer program based on the two-compartment model. It is shown that during pregnancy complicated by UTI the elimination half-life time will be prolonged and returns after therapy nearly to normal values. The results, discussed with the dates given by literature, allow us to state that it is not necessary to change dosage and application interval of azlocillin during pregnancy.

In 72 pregnant women with culture-proved vaginal candidiasis, and an equal number of controls matched for parity, size, stage of gestation and age, the intravenous glucose tolerance curves were compared using Silverstone's method. The results in both study and control groups did not differ and resembled closely those in Silverstone's series. Half the study group were treated using nystatin alone, while the other half also received tolbutamide. The cure rate was equal in the two groups. Candidiasis in pregnancy does not appear to be related to altered glucose metabolism nor does the addition of this hypoglycemic drug (tolbutamide) improve results. No ill effects, fetal or maternal, were apparent following the use of tolbutamide.