COMPARISON OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ORAL DOSES OF PERINDOPRIL IN NORMOTENSIVE CHINESE AND CAUCASIAN VOLUNTEERS

1 The pharmacokinetics of perindopril and perindoprilat and the hormonal and haemodynamic responses following a single oral dose were studied in 12 Chinese and 10 Caucasian healthy, normotensive volunteers on two occasions. Perindopril was given on the first occasion as a 4 mg dose and then after at least 10 days as a weight-adjusted dose of 4 mg/70 kg. Plasma was sampled for assay of perindopril, perindoprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE activity. Urine was collected for perindopril and perindoprilat assay. A radioimmunoassay technique was used to measure the prodrug and its active metabolite. 2 The time to maximum concentration (t(max)) for perindopril was shorter for the Chinese group after the 4 mg dose (median 0.5, range 0.5-1.5 h vs median 1.0, 0.5-1.5 h P < 0.05) and also tended to be shorter after the weight-adjusted dose (median 0.5, range 0.5-1.0 h vs median 1.0, range 0.5-3.0 h). C-max and AUC tended to be higher after the 4 mg dose in the Chinese group who had a lower body weight than the Caucasians. 3 The t(max) of perindoprilat tended to be shorter for both doses and there was a tendency towards a higher C-max after the 4 mg dose in the Chinese group but there was no statistically significant difference between the two groups. 4 There were no differences in the levels of PRA, plasma AI, plasma aldosterone or the degree of ACE-inhibition for either dose in the two ethnic groups. 5 Blood pressure was measured at intervals up to 24 h post-dose in both the supine and standing positions. Perindopril reduced blood pressure acutely with respect to the pre-dose level with good tolerability in both groups. 6 The pharmacokinetics of perindopril are essentially the same in Chinese and Caucasians although absorption of the prodrug and conversion to the active metabolite appeared to be more rapid in the Chinese group. However, there were no differences in its hormonal or haemodynamic effects and no alteration of the standard dose of 4 mg appears to be necessary for Chinese subjects.