The stable isotope method for determining absolute bioavailability

Abstract

The bioavailability of a drug is usually assessed in healthy subjects. However, it is reasonable to expect that significant alterations in bioavailability may occur in actual patients with different diseases or in individuals belonging to special populations. Relatively few studies have been conducted to examine this possibility. The stable isotope method is well suited to compare absolute bioavailability in patients and healthy subjects. Studies in which this method was used indicate that significant changes in the bioavailability of some drugs are particularly likely in patients with advanced liver disease and in those whose splanchnic blood flow is reduced. The expectation is that bioavailability in neonates, children, and pregnant women may also differ from that in non-pregnant adults.

Keywords: Absolute bioavailability; Patient studies; Pharmacokinetics; Stable isotopes.

Figure 1. Relationship between bioavailability and CL_F as an indirect indicator of splanchnic blood flow. Absorption of NAPA was reduced in both healthy subjects (■) and patients (■) with CL_F less than 1.1 L/min (p = .0286, Fisher's exact test). (Data from Strong et al. (2) and Atkinson et al. (20)).