The pharmacokinetic properties of the developmental Amino-Acetonitrile Derivative (AAD), monepantel and its sulfone metabolite, monepantel sulfone were investigated in sheep following intravenous (i.v.) and oral administrations. The sulfone metabolite was rapidly formed and predominated over monepantel 4 h after dosing, irrespective of the route of administration. The steady-state volume of distribution, total body clearance and mean residence time of monepantel were 7.4 L/kg, 1.49 L/(kg x h) and 4.9 h, respectively and 31.2 L/kg, 0.28 L/(kg x h) and 111 h, respectively for monepantel sulfone. The overall bioavailability of monepantel was 31%, but it was demonstrated that approximately the same amount of monepantel sulfone was produced whether monepantel was given intravenously or orally (AUC((0-infinity)) oral/AUC((0-infinity)) i.v. of 94% for monepantel sulfone), making oral administration a very efficient route of administration for monepantel in terms of the amount of sulfone metabolite generated. Because monepantel sulfone is the main chemical entity present in sheep blood after monepantel administration and because it is also an active metabolite, its pharmacokinetic properties are of primary importance for the interpretation of future residue and efficacy studies. Overall, these pharmacokinetic data aid in the evaluation of monepantel as an oral anthelmintic in sheep.

Summary The placental transfer of cefuroxime was studied in 20 women after one or more 1.5 g intravenous injections. Ten women had labour induced at term and ten were delivered by elective Caesarean section. High concentrations of cefuroxime were found in the cord blood and amniotic fluid and therapeutically active antibiotic levels were found in the infants for up to six hours after delivery.

Pharmacokinetics of cefuroxime was studied in patients on continuous ambulatory or intermittent peritoneal dialysis. A single intravenous bolus (15 mg/kg) of cefuroxime provided a mean serum concentration of 86 mg/litre 5 min, 40 mg/litre 1 h, 163 mg/litre 24 h after the injection. The peritoneal clearance of cefuroxime varied widely among different individuals, ranging from 1.45 to 6.17 ml/min with a mean of 3.59 ml/min during 4-hour exchanges, and from 0,52 to 11.3 ml/min during 2-hour exchanges. A single injection (15 mg/kg) of the antibiotic could not provide satisfactory antibiotic concentrations in peritoneal effluent during peritoneal lavage. When cefuroxime had been added to peritoneal dialysis solution before the solution was instilled into the peritoneal cavity, a significant decrease in cefuroxime concentration occurred in the peritoneal effluent even after a short equilibration time. Furthermore, cefuroxime concentrations measured in residual dialysis solutions in the plastic bags ranged from 44.3 to 1,351% of the concentration of cefuroxime calculated from the added doses, indicating that despite great care, mixing of the antibiotic with dialysis solutions in plastic bags was far from uniform.

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