Meperidine disposition in man: Influence of urinary pH and route of administration

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Abstract
The effects of route of administration and altered urinary pH on the disposition of meperidine and its metabolite normeperidine were investigated in 6 normal, nonsmoking young men from 23-31 yr old. Meperidine (21.75 mg) was injected i.v. simultaneous with the same dose of deuterated (2H5) drug given orally in solution or by injection into the deltoid muscle. After i.v. administration with no control of urinary pH, meperidine blood levels declined triexponentially over 24 h with a terminal half-life (t1/2) of 4.9-9.4 h and a clearance of 472-686 ml/min. The 48 h urinary recoveries of meperidine and normeperidine were .apprx. 7% and 12%. Urinary acidification with ammonium chloride reduced these amounts to < 1% and .apprx. 7%, whereas urinary alkalinization increased them to .apprx. 20% and 24%. These pronounced changes had negligible effects on the blood concentration/time profiles. Plasma levels were proportional to the blood concentrations with a ratio of about unity for meperidine and a value 25% greater for normeperidine. Absorption after i.m. injection was complete and followed a first-order process with t1/2 ranging from 7-13 min. Accordingly, maximum blood levels were achieved within 5-15 min and the concentration was essentially the same as after i.v. dosing. In contrast, oral bioavailability was incomplete, ranging from 47-73%, and at a much slower rate, with peak concentrations being observed after .apprx. 1 h. Absorption was biphasic and was preceded by a 5-10 min lag period. Normeperidine blood concentration after i.v. dosing reached a maximum within 2-4 h and remained at this value through 12 h before modestly declining by 24 h. After oral dosing the peak level was achieved more rapidly and sharply. Thus, presystemic elimination occurs after oral dosing with meperidine consistent in value with the measured blood clearance which probably reflects only hepatic metabolism.

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