Labetalol disposition and concentration-effect relationships during pregnancy.

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Abstract
1 Labetalol pharmacokinetics and concentration‐effect relationships following intravenous administration have been studied in 10 women during the last trimester of pregnancies complicated by hypertension, in seven of these women postpartum (when normotensive) and in 10 normotensive female volunteers. 2 The clearance and volume of distribution of labetalol were the same in all three groups. Clearance values (1 min‐1) were: pregnant, 2.16 (range 1.54‐3.14); postpartum 2.35 (1.56‐3.85); controls 1.96 (0.98‐2.61). Volumes of distribution (1) were: pregnant 274 (250‐547); postpartum 407 (248‐701); controls 234 (186‐415). 3 A linear model relating labetalol concentration to effect successfully described the antihypertensive action of labetalol in the pregnant patients. Supine systolic blood pressure fell by 0.38 (0.14‐0.91) mm Hg per ng ml‐1 of labetalol and diastolic by 0.36 (0.21‐ 1.14) mm Hg per ng ml‐1 of labetalol. In the other two groups labetalol did not lower pressure sufficiently to allow modelling to be performed. 4 We conclude that pregnancy does not alter the clearance or volume of distribution of labetalol. Modelling techniques can be applied successfully to drug induced blood pressure changes during pregnancy.

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