Nifedipine Kinetics and Bioavailability After Single Intravenous and Oral Doses in Normal Subjects

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Abstract
Nifedipine kinetics have not been described in clinically relevant detail because of difficulties in formulating a stable preparation for intravenous use and lack of a specific and sensitive assay for plasma nifedipine. We recently developed a gas‐chromatographic method and determined conditions in which nifedipine could be protected from photodegradation. Therefore, we evaluated the kinetics and bioavailability of nifedipine in 12 normal subjects after single intravenous (1 mg/5 min) and oral (10 mg) doses. After intravenous dosing, the drug was eliminated with a half‐time of 1.77 ± 0.25 hour, and total clearance was calculated at 0.62 ± 0.09 liter/kg/hr. With oral drug administration, the elimination half‐time was twice as long for the group; but within these subjects, marked variability in the rate of appearance of the drug in plasma was observed, giving profiles consistent with fast and slow absorption. In the latter group, peak plasma drug concentrations were only one third the level seen in those exhibiting a faster absorption profile, although the extent of drug absorption (as derived from areas under the plasma level‐time curves) did not vary. Bioavailability was 0.45 ± 0.08. Untoward effects resulting from the drug's pharmacologic activity was observed in five of the subjects after oral drug (headache) and three subjects after intravenous administration (flushing).