Reabsorption and metabolism of quinapril and quinaprilat in rat kidney: in vivo micropuncture studies.
The tubular uptake and esterolysis of quinapril and quinaprilat were studied in male Sprague-Dawley rats using an in vivo micropuncture technique. [3H]Quinapril or [3H]quinaprilat was injected with [14C]inulin into either proximal or distal segments of the renal tubules, and urine was collected over 30 min. Urine and perfusate were assayed for [14C]-inulin using dual label spectrometry. [3H]Quinapril and [3H]quinaprilat concentrations were determined in urine and perfusate using a reversed-phase HPLC procedure with radiochemical detection, coupled to liquid scintillation spectrometry. These studies demonstrated that quinapril could access the esterase enzyme from tubular fluid and be metabolized to quinaprilat in both proximal and to a lesser extent distal segments of the kidney tubule. Quinapril, but not quinaprilat, was extensively reabsorbed. Its reabsorption along the proximal tubule and/or the loop of Henle could account for as much as 45-50% of the available dose of quinapril. Further, the urinary recovery of quinapril and quinaprilat (after dosing quinapril into proximal segments) was urine flow rate dependent.
Smith
D E
DE
College of Pharmacy, University of Michigan, Ann Arbor 48109-0504, USA.
Kugler
A R
AR
Schnermann
J B
JB
D000042:Absorption; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D000818:Animals; D007546:Isoquinolines / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008845:Microinjections; D009399:Nephrons / Q000378:metabolism; D011355:Prodrugs / Q000378:metabolism* / Q000493:pharmacokinetics; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D044005:Tetrahydroisoquinolines; D014563:Urodynamics
D000806:Angiotensin-Converting Enzyme Inhibitors; D007546:Isoquinolines; D011355:Prodrugs; D044005:Tetrahydroisoquinolines; C054501:quinaprilat; D000077583:Quinapril