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PubMed1989

First-pass uptake of verapamil, diazepam, and thiopental in the human lung.

The first-pass uptake of verapamil, diazepam, and thiopental in the human lung was determined using multiple-indicator dilution techniques. These three drugs represent lipid-soluble agents that differ in their ionic characteristics at physiological pH. Verapamil, a basic lipophilic amine, underwent significant uptake, with 50% of the drug accumulating in lung tissue during the first pass. With diazepam, a nonbasic lipophilic amine, there was 30% uptake during the first pass through the human lung--significantly less than that observed with verapamil. With thiopental, an acidic lipophilic barbiturate, only 14% of the injected drug accumulated in the lung during the first pass. Taken together, these data are consistent with observations from animal studies, which indicate that extensive pulmonary uptake is greater with basic amine drugs that are moderately to highly lipid-soluble. Also, the relatively high first-pass uptake of verapamil in the human lung suggests a quantitatively significant role of this nonrespiratory function of the lung in the early pharmacokinetics of intravenous verapamil.

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