No abstract

No abstract

The pharmacokinetics of the beta 1-selective adrenergic antagonist (R,S)-celiprolol has been studied after oral administration of 200 mg celiprolol-HCl to 8 healthy volunteers and 8 patients with various degrees of impaired renal function. No significant difference was found between the two enantiomers in the control group or in the patients. In healthy volunteers an average of 9.8% of the dose of R-(+)-celiprolol and 9.5% of S-(-)-celiprolol was recovered unchanged in the urine. Renal impairment reduced the urinary excretion of both enantiomers to the same extent according to the severity of the uraemia, producing higher AUCs. Nevertheless, the terminal half-lives of the R- and S-enantiomers were not significantly different between the groups. Dosage reduction in patients with renal impairment does not seem to be necessary.

A method is described for the quantification of baclofen enantiomers in biological material (urine, plasma, and cerebrospinal fluid). The samples were extracted by liquid-solid extraction using Sep-Pak C18 cartridges. The subsequent derivatization procedure contained two separate steps. (1) The butyl esters of the enantiomers were formed using butanolic hydrochloric acid (followed by ion-pair extraction of the intermediate products). (2) A chiral derivatization was then performed using S-(+)-naproxen chloride as reagent. S-(+)-Benoxaprofen chloride can also be used. The diastereomeric amides were separated by high-performance liquid chromatography (HPLC) on a silica gel column (mobile phase, n-hexane/dichloromethane/ethanol; detection, fluorescence measurement at 335/365 nm). The described procedure was also used for the quantification of the fluoro analogue of baclofen. Urinary excretion of baclofen enantiomers was investigated in two healthy volunteers after p.o. administration.

atenolol (TenorminR) once daily over a period of 7 days. The remaining 6 volunteers received metoprolol 100 mg (LopresorR) twice daily over 7 days. After a therapy-free interval of 2 days, 20 mg of piroxicam (FeldenR), were given twice daily together with the P-antagonist for 7 days. After the morning dose on day 7 the elimination kinetics of the P-receptor antagonists were studied. Blood sampling times: on the lst, 2nd, 3rd and 6th day of each of the treatment periods: before and 2 hours after the morning dose, on the 7th and 8th day: before, I, 2,3,4,6, 12,24, and 48 hours after the last administration (day 7). Blood (heparin-treated) was centrifuged immediately, and the plasma was stored frozen (-20 "C) until analysis. Urine was collected up to 24 hours after the morning dose on day 7. Assay methods