Eleven patients with severe, treatment-resistant essential or renovascular hypertension were treated with captopril after withdrawal of various multiple drug regimes. If supine diastolic blood pressure remained greater than 90 mm Hg on a maximum daily dose of 450 mg captopril, a diuretic and then a beta-adrenoceptor blocker were added. Patient-volunteered complaints were carefully noted. Mean (+/- SE) systolic and diastolic blood pressures fell from 225 +/- 6.8/131 +/- 4.4 mm Hg on various multiple drug regimes to 182 +/- 9.0/105 +/- 5.0 mm Hg on a regime including captopril. The reported and observed incidence of adverse effects were as follows: maculopapular rash (one patient); urticaria and pruritus (three patients); loss of taste (one patient); tachycardia (four patients); increased frequency of trivial infections (three patients); severe myalgia (one patient); and deterioration in renal function (one patient). However, these patients were able to continue captopril after either temporary withdrawal or dose reduction. Captopril was discontinued permanently in five patients, in two because of poor blood pressure control, in one who developed persistent severe urticaria, and in one because of marked proteinuria. In the fifth patient intractable diarrhoea occurred. Captopril lowers blood pressure very effectively in patients with severe hypertension refractory to other agents. Adverse effects are common but acceptable in this situation where prognosis is poor if blood pressure is not adequately controlled.

Adult↗

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Clinical pharmacokinetics of oral contraceptive steroids.

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Disposition of pethidine in man under acidic urinary pH. 4. Kinetics after oral dose in caucasian, Chinese and Indian subjects.

The pharmacokinetics of low dose pethidine (450 micrograms kg-1) after oral administration were determined in 9 Caucasian, 9 Chinese and 9 Indian healthy volunteers under conditions of acidic urinary pH. Plasma and urine concentrations of pethidine and norpethidine were determined simultaneously by gas liquid chromatography. In all three ethnic groups the oral absorption of pethidine was rapid. The Tmax was faster in the Caucasian group (0.75 h) compared with the Chinese group (1.0 h) and the Indian group (1.5 h). No significant difference was observed in their respective lag time while the absorption t1/2 was significantly shortest in the Caucasian group who also had the highest Cmax (95.5 +/- 7.8 ng ml-1) compared with the Chinese (85.9 +/- 11.0 ng ml-1) and the Indian (58.2 +/- 3.0 ng ml-1) groups. Moderate exercise and upright posture of the Asian students might interfere with absorption and distribution of pethidine, due possibly to change in blood flow during the early stage of the study while the Caucasian subjects were in supine position. No significant difference was observed in the elimination t1/2 of pethidine between the Caucasian (8.3 +/- 0.2 h) and the Chinese (8.2 +/- 0.2 h) groups, although the Indian subjects significantly had the longest elimination t1/2 (0.1 +/- 0.3 h); this could possibly be due to their significantly higher apparent volume distribution. Under acidic urinary conditions both Chinese and Indian subjects excreted significantly more norpethidine in the urine while no difference was observed in the recovery of unchanged pethidine; this may suggest an interethnic difference in the oxidative demethylation of pethidine.

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