Dalton J T, Harrington M D, Au J L
College of Pharmacy, Ohio State University, Columbus 43210.
J Pharmacol Exp Ther. 1992 Feb;260(2):608-13.
We examined the in vivo absorption and pharmacokinetics of antipyrine, a base that is unionized at physiologic pH, from the urinary bladder of adult female Fischer rats. The clearance of an i.v. dose of antipyrine (25 mg/kg) was found to vary considerably between animals, which is consistent with the literature data. Therefore, it was necessary to simultaneously determine drug clearance and bladder absorption in the same animal. This was accomplished by giving concomitantly an i.v. dose of [14C]antipyrine (2.5 muCi, about 90 micrograms/kg) via a jugular vein catheter and an intravesical dose of unlabeled antipyrine (33 mg/kg) via a urethral catheter. Unlabeled antipyrine was detected in plasma, indicating the absorption of antipyrine into systemic circulation. The bioavailability of the intravesical dose was calculated using the clearance of [14C]antipyrine and the plasma concentrations of unlabeled antipyrine. The intravesical dose was withdrawn through the urethral catheter after 90 min. To minimize mechanical manipulation and damage, the bladder was not rinsed. This may have caused the incomplete recovery of the unabsorbed dose; about 65 +/- 18% (mean +/- S.D.) of the dose was recovered at 90 min. Maximal plasma concentrations were achieved at 10 to 48 min after removal of the intravesical dose, which is consistent with a continued absorption of the residual dose. The intravesical bioavailability was variable between animals, with an average of 11.6 +/- 6.4% (mean +/- S.D.; range, 4.1-19.2%). In conclusion, these data demonstrate that neutral drugs such as antipyrine are absorbed from the bladder, that the extent of absorption is variable and that the urinary bladder may be a site of significant re-entry of drugs into the systemic circulation.
我们研究了安替比林（一种在生理pH下呈非离子化状态的碱）在成年雌性Fischer大鼠膀胱内的体内吸收及药代动力学情况。静脉注射一剂安替比林（25mg/kg）后，发现不同动物之间的清除率差异很大，这与文献数据一致。因此，有必要在同一只动物身上同时测定药物清除率和膀胱吸收情况。通过经颈静脉导管静脉注射一剂[14C]安替比林（2.5μCi，约90μg/kg）并经尿道导管膀胱内给予一剂未标记的安替比林（33mg/kg）来实现这一点。血浆中检测到未标记的安替比林，表明安替比林吸收进入了体循环。使用[14C]安替比林的清除率和未标记安替比林的血浆浓度计算膀胱内给药剂量的生物利用度。90分钟后通过尿道导管抽出膀胱内给药剂量。为尽量减少机械操作和损伤，未冲洗膀胱。这可能导致未吸收剂量回收不完全；90分钟时约65±18%（均值±标准差）的剂量被回收。去除膀胱内给药剂量后10至48分钟达到最大血浆浓度，这与残留剂量的持续吸收一致。不同动物之间膀胱内生物利用度存在差异，平均为11.6±6.4%（均值±标准差；范围4.1 - 19.2%）。总之，这些数据表明像安替比林这样的中性药物可从膀胱吸收，吸收程度存在差异，且膀胱可能是药物大量重新进入体循环的部位。
