1 Six lactating white women, aged 24-36 years, received a single oral dose of 300 mg moclobemide, between 09.00 h and 11.00 h, 3 to 5 days after the delivery of a full term neonate. 2 Complete milk collections were obtained before, 3, 6, 9, 12 and 24 h after drug administration by means of a breast pump. Venous blood samples were drawn before, and 0.5, 1, 3, 4.5, 6, 9, 12, 24 h post-dosing. 3 Moclobemide, and its major metabolite (Ro 12-8095) were measured in milk and plasma samples using h.p.l.c. The active metabolite (Ro 12-5637) could only be detected in plasma. 4 Moclobemide and its metabolites were not detectable in 24 h plasma samples. Cmax, tmax and t½h for moclobemide were (mean ± s.d.) 2.70 ± 1.24 mg l-1, 2.03 ± 1.19 h and 2.26 ± 0.26 h, respectively. 5 The concentrations of moclobemide and Ro 12-8095 in milk were highest at 3 h after drug administration and the drug and metabolite were not detectable after 12 h. Ro 12-5637 was not detected in any milk sample. The percentages of the dose excreted as moclobemide and Ro 12-8095 were (mean ± s.d.) 0.057 ± 0.020% and 0.031 ± 0.011%, respectively. An average 3.5 kg breast-fed neonate would therefore be exposed to only a 0.05 mg kgmoclobemide dose (approximately 1% of the maternal dose on the mg kg-' basis).

The disposition of metoclopramide was studied on a four-way crossover basis in six healthy non-smoking volunteers. The linearity of kinetic parameters and absolute bioavailability of metoclopramide were examined. In contrast to previous reports, metoclopramide obeyed linear kinetics over oral doses ranging from 5 to 20 mg. The absolute bioavailability of metoclopramide was 0.76 ± 0.38 (mean ± s.d.) from the oral dosage forms examined in this study.

The pharmacokinetics of cefetamet after a short intravenous infusion of cefetamet (515 mg) and oral administration of 1,000 mg of cefetamet pivoxil were studied in 9 healthy subjects and in 38 patients with various degrees of renal impairment. The results showed that cefetamet elimination was dependent on renal function. After intravenous dosing, total body (CLs), renal (CLR), and nonrenal (CLNR) clearances were linearly related to creatinine clearance (CLCR; r = 0.95, 0.92, and 0.59, respectively). Elimination half-life (t112^) was prolonged from 2.46 ± 0.33 h in normal subjects to 29.1 13.9 h in patients with CLCR of <10 ml/min per 1.73 i2. Correspondingly, CLs and CLR decreased from 1.77 0.27 and 1.42 0.25 mI/mi per kg to 0.14 + 0.04 and 0.04 + 0.03 ml/min per kg, respectively. The volume of distribution at steady state (0.298 0.049 liter/kg) for cefetamet was not altered by renal insufficiency (P > 0.05). After oral administration, the elimination parameters, tl/2,, and CLR, were insignificantly different from the intravenous data (P > 0.05).Furthermore, the bioavailability (F) of cefetamet pivoxil (45 13%) was not altered by renal failure (P > 0.05). However, maximum concentration in plasma and the time to achieve this value were significantly increased (5.86 0.74 versus 14.8 6.14 ,ug/ml and 3.9 ± 1.1 versus 8.4 1.7 h, respectively; P < 0.05).Based on these observations, it is recommended that patients with CLCR of <10 ml/min per 1.73 m2 and between 10 and 39 ml/min per 1.73 m2 be given one-quarter of the normal daily dose either once or twice daily.Patients with CLCR between 40 and 80 ml/min per 1.73 m2 should receive one-half of the normal dose twice daily. For patients with CLCR of <10 ml/min per 1.73 m2, it would be recommended that they receive a normal standard dose as a loading dose on day 1 of treatment.Cefetamet pivoxil is the prodrug (pivaloyloxymethylester) of a new broad-spectrum cephalosporin antibiotic, cefetamet. This compound possesses a broad spectrum of antimicrobial activity against many aerobic gram-positive and gram-negative organisms (19). Previous pharmacokinetic studies in normal healthy volunteers revealed that the lowprotein-bound (22%) cefetamet is mainly eliminated by the kidneys via glomerular filtration (2, 12). This kinetic behavior is similar to that of other P-lactam antibiotics with low protein binding and high urinary recovery (e.g., carumonam [11], ceftizoxime [1,15], and ceftazidime [1,15]). Consequently, the pharmacokinetics of cefetamet are expected to be dependent on changes in renal function.The objectives of this study were to determine the pharmacokinetics of cefetamet and cefetamet pivoxil after intravenous and oral administration to patients with various degrees of impaired renal function, to compare these results with those obtained from healthy volunteers who have normal renal functions, and to determine dosage guidelines for patients with renal impairment. MATERIALS AND METHODSSubjects. Nine healthy volunteers (7 men and 2 women) and 38 patients (22 men and ...

Flunitrazepam in 2-mg and 4-mg doses was compared with flurazepam 30 mg and nitrazepam 10 mg for hypnotic efficacy in a double-blind, multiple cross-over trial involving 41 psychiatric in-patients. In the vast majority of comparisons involving a number of sleep parameters differences did not reach significance level. Flunitrazepam 4 mg tended to produce the shortest latency time and the longest duration of sleep but also the most side-effects. Nitrazepam 10 mg appeared to have a slight advantage over the other drugs in terms of patient preference. For severe sleep disturbance flunitrazepam 2 mg tended to be the most satisfactory drug in terms of efficacy and paucity of side-effects.