Determination of debrisoquine metabolic ratio from hourly urine collections in healthy volunteers.

Abstract

The possibility of simplifying the regimen for the collection of urine samples in the determination of the debrisoquine metabolic ratio (DMR) was explored in 15 normal subjects. In the extensive metaboliser subgroup (EM; n = 11), there was a close correlation between the DMR as determined by an 8 h urine collection and the debrisoquine/4-hydroxydebrisoquine ratio (D/4-OHD) in the hourly samples (excluding the first hour). In the poor metabolisers (PM; n = 4) the phenotype could be identified, but it was not possible to estimate the DMR reliably.

Debrisoquine oxidation phenotype and susceptibility to lung cancer [letter; comment]

“…The time of drug administration does not affect the phenotype, or the metabolic ratio (Lee, 1988). Indeed, the metabolic ratio is stable from 1 h to at least 24 h after administration of debrisoquine (Philip et al, 1987; Caporaso and Idle suggest that the analytical method used in our study might have biased the results. There is no question of the precision or sensitivity of the combined gas chromatographymass spectrometry (GC-MS) method utilised to determine debrisoquine and its 4-hydroxy metabolite (Murray & Waddell, 1982).…”

“…No evidence is provided for this, and indeed the literature would suggest the contrary. The absolute phenotype, as opposed to the metabolic ratio, appears to be a relatively robust parameter and in extensive studies by groups such as Philip et al (1987), Steiner et al (1988 and Lee (1988), as well as by ourselves, it has been possible to demonstrate that the changes to the protocol used by Idle and colleagues do not materially affect the metabolic ratio, let alone the phenotype. These include reducing the dose of debrisoquine from 12.8 mg to 1 mg (Speirs et al, 1986); Idle and his colleagues themselves have shown that there is no saturation of this pathway at doses less than 20 mg in extensive metabolisers (Idle et al, 1978).…”

“…Thus, the only disadvantage of using this method is that absolute recoveries of debrisoquine and its metabolite cannot be determined. However, assignment of phenotype does not depend upon fractional recovery of debrisoquine and its 4-hydroxy metabolite in urine and certainly is not dependent upon the amount of debrisoquine or its metabolite present in the sample, as long as the assay utilised has sufficient sensitivity (Boobis et al, 1987;Philip et al, 1987), an advantage of utilising a GC-MS method in such studies.…”