A double blind crossover trial of baclofen against placebo in elderly stroke patients was discontinued because the drug produced an unacceptably high level of drowsiness. In a subsequent study baclofen 10 mg was given orally to 12 elderly stroke patients, and drug concentrations measured from a series of plasma samples. A group of healthy subjects given the same dose in a previous study were used as controls. Elderly patients took longer to achieve peak plasma baclofen concentrations, but healthy controls had higher peak values and eliminated the drug more rapidly; areas under the curve were similar in the two groups. Simulations based on mean data suggest that increased drowsiness in the elderly was probably not due to changes in the drug's pharmacokinetic behaviour.
1 Effects of rifampicin on the pharmacokinetics of single oral doses of metoprolol and antipyrine are reported. 2 Rifampicin, administered daily for 15 days, reduced the area under the plasma concentration‐time curve (AUC) of metoprolol but the rate constant for elimination (beta) of metoprolol from plasma did not alter significantly. 3 Administration of rifampicin for 13 days reduced AUC and increased beta of antipyrine. Thirteen days after discontinuing rifampicin. AUC and beta of antipyrine remained significantly different from the initial values. 4 Some loss of beta‐adrenoceptor blockade should be anticipated if rifampicin is administered to patients who are receiving metoprolol.
1. Plasma drug concentrations after a single oral administration of a suspension of carbamazepine (CBZ) and a 20/200 CBZ Oros osmotic pump system were measured in eight healthy male volunteers. The oral suspension contained 100 mg CBZ labelled with the stable isotope nitrogen‐15, whilst the Oros contained 200 mg unlabelled CBZ. Plasma concentrations of [15N]‐CBZ and CBZ were measured simultaneously by gas chromatography‐mass spectrometry. 2. The position of the CBZ Oros (labelled with indium‐111) in the gastrointestinal tract was followed by gamma scintigraphy. Plasma drug concentrations after the two treatments were used to relate pharmacokinetic with transit data. 3. The Oros was taken after breakfast and gastric emptying occurred between 1.1‐ greater than h post‐dosing (median, 5.3 h). Small intestinal transit times ranged from 1.5‐ greater than 3.6 h, with a median of 2.2 h. There were wide individual variations in colonic transit, and the total transit time ranged from 10‐60 h (median, 22 h). 4. Relative systemic bioavailability of CBZ from the Oros was reduced compared with that from the suspension (mean dose normalised AUC ratio = 0.69 +/‐ 0.17; mean dose‐normalised AUC ratio = 0.85 +/‐ 0.13, allowing for actual release from the Oros system). 5. The in vivo absorption of drug into the systemic circulation from the Oros was estimated using the Wagner‐Nelson method. This showed that absorption of CBZ was rapid when the Oros was present in the stomach and small intestine, the rate being determined by the release of drug from the system.(ABSTRACT TRUNCATED AT 250 WORDS)
2 Variations in mean plasma levels and P-adrenoceptor blockade (measured by inhibition of exercise tachycardia) were considerably reduced on the 10/170 Oros once-daily compared with the Trasicor 80 mg twice-daily regimen. With both formulations there was no significant change in mean plasma concentrations or areas under the curve after 8 days' treatment, and similar pre-dose plasma concentrations were obtained. There was significant inhibition of exercise tachycardia throughout 24 h after the 10/170 Oros on the eighth day. 3 The 16/260 Oros system gave smoother pharmacokinetic and pharmacodynamic profiles, and on repeated dosing a higher mean pre-dose plasma oxprenolol concentration than Slow Trasicor. Drug availability was similar for the two dose forms, suggesting an acceptable level of absorption of oxprenolol from most of the gastrointestinal tract. On the eighth day exercise heart rate was significantly reduced throughout 24 h with 16/260 oxprenolol Oros, but only between 1 and 15 h with Slow Trasicor.
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