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- W2098833304 abstract "The effects of route of administration and altered urinary pH on the disposition of meperidine and its metabolite normeperidine were investigated in six normal, nonsmoking young men from 23 to 31 yr old. Meperidine (21.75 mg) was injected intravenously simultaneous with the same dose of deuterated (2H5) drug given orally in solution or by injection into the deltoid muscle. After intravenous administration with no control of urinary pH, meperidine blood levels declined triexponentially over 24 hr with a terminal half-life (t½) of 4.9 to 9.4 hr and a clearance of 472 to 686 ml/min. The 48-hr urinary recoveries of meperidine and nonneperidine were about 7% and 12%. Urinary acidification with ammonium chloride reduced these amounts to less than 1% and about 7%, whereas urinary alkalinization increased them to about 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 nonneperidine. Absorption after intramuscular injection was complete and followed a first-order process with t½ ranging from 7 to 13 min. Accordingly, maximum blood levels were achieved within 5 to 15 min and the concentration was essentially the same as after intravenous dosing. In contrast, oral bioavailabilitv was incomplete, ranging from 47% to 73%, and at a much slower rale, with peak concentrations being observed after about 1 hr. Absorption was biphasic and was preceded by a 5- to 10-min lag period. Nonneperidine blood concentration after intravenous dosing reached a maximum within 2 to 4 hr and remained at this value through 12 hr before modestly declining by 24 hr. 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, therefore, probably reflects only hepatic metabolism. Clinical Pharmacology and Therapeutics (1981) 30, 619–628; doi:10.1038/clpt.1981.213" @default.
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- W2098833304 date "1981-11-01" @default.
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- W2098833304 title "Meperidine disposition in man: Influence of urinary pH and route of administration" @default.
- W2098833304 doi "https://doi.org/10.1038/clpt.1981.213" @default.
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