Department of Clinical Pharmacology, Ernst Moritz Arndt University, Friedrich-Loeffler-Str. 23d, D-17487 Greifswald, Germany.
J Clin Pharmacol. 2012 May;52(5):681-90. doi: 10.1177/0091270011401260. Epub 2011 May 6.
The muscarinic receptor antagonist propiverine is unique insofar as extended-release (ER) tablets are of higher bioavailability than immediate-release (IR) tablets; this is caused by lower "first-pass" elimination of propiverine via CYP3A4 and efflux transporters in the distal small intestine and colon. Food may influence gastrointestinal transiting and, in turn, may affect regional absorption of propiverine IR and ER. Therefore, food effects on disposition of 30 mg IR and 45 mg ER were measured in a randomized, open, 4-period interaction study in 24 healthy participants. In fasting participants, ER had higher bioavailability than IR (F(rel) = 169%, P = .03). Fat-rich meal did not change the disposition of ER markedly (AUC(0-∞) ratio, 1.00 [90% confidence interval (CI), 0.90-1.11], C(max) ratio, 0.97 [0.87-1.09]). However, C(max) and renal A(e) of the major N-oxidized metabolite (M-5) significantly increased, whereas t(1/2) decreased. By eating a fat-rich meal before administration, the differences in absorption of IR and ER were nearly abolished (AUC(0-∞) ratio for propiverine, 1.12 [90% CI, 0.95-1.33]; AUC(0-∞) ratio for M-5, 0.89 [0.82-0.95]). In conclusion, propiverine ER has higher bioavailability than IR and no positive food effect because it reaches, independently of food, intestinal absorption areas with lower metabolism and efflux transport, which results in constant absorption rates.
抗毒蕈碱受体拮抗剂丙哌维林的特点是，其缓释片的生物利用度高于速释片；这是由于丙哌维林通过 CYP3A4 和远段小肠及结肠中的外排转运体的“首过”消除率降低所致。食物可能会影响胃肠道转运，进而可能会影响丙哌维林速释和缓释片的局部吸收。因此，在 24 名健康参与者中进行了一项随机、开放、4 周期相互作用研究，以评估食物对 30mg 速释片和 45mg 缓释片处置的影响。在禁食参与者中，缓释片的生物利用度高于速释片（F(rel) = 169%，P =.03）。高脂肪餐并未明显改变缓释片的处置（AUC(0-∞) 比值，1.00[90%置信区间（CI），0.90-1.11]；C(max)比值，0.97[0.87-1.09]）。然而，主要 N-氧化代谢产物（M-5）的 C(max)和肾 A(e)显著增加，而 t(1/2)缩短。进食高脂肪餐会使速释和缓释片的吸收差异几乎消失（丙哌维林的 AUC(0-∞)比值，1.12[90%CI，0.95-1.33]；M-5 的 AUC(0-∞)比值，0.89[0.82-0.95]）。总之，丙哌维林缓释片的生物利用度高于速释片，且不受食物的影响，因为它独立于食物到达代谢和外排转运较低的肠吸收部位，从而导致吸收速率恒定。
