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Perindopril, an orally active angiotensin converting enzyme (ACE) inhibitor, was fed by gavage to male Sprague-Dawley rats. The effect on tissue ACE was measured ex vivo by quantitation of binding of the specific radioligand 125I-3511A to ACE in tissue homogenates. In an acute time-course study perindopril (1, 4 or 8 mg/kg) inhibited plasma ACE activity by more than 90% in 1 h but no inhibition remained after 24 h. Kidney ACE was affected to a similar degree and followed a similar time-course of inhibition to plasma ACE. In contrast, ACE was inhibited to a lesser degree in lung and aorta homogenates, with maximum effect 4-8 h postgavage, and with inhibition persisting 48 h following the dose. In testis homogenates, ACE remained unaltered following the administration of perindopril at all three doses. Therefore we conclude that plasma ACE inhibition does not parallel tissue effects, and that drug penetration into the testis appears to be limited. |
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