1 The N-acetylation of dapsone (DDS) was studied in 160 unrelated healthy Jordanian volunteers. 2 The frequency of slow acetylators determined using the plasma monoacetyldapsone (MADDS) to DDS ratio (MADDS/DDS), was 67.5% with a 95% confidence interval of 59 to 76%. Slow acetylators had an acetylation ratio of < 0.42. 3 Applying the Hardy-Weinberg Law, the frequency of the recessive allele controlling slow acetylation was found to be 0.82 ± 0.02. 4 The frequency distribution histogram of the plasma MADDS/DDS ratio showed an apparent trimodal pattern. The number of homozygous (n = 16) and heterozygous (n = 36) rapid acetylators derived from the observed data did not agree with those predicted for the respective rapid acetylators (n = 5 and n = 47) according to the Hardy-Weinberg Law. The suggested antimode used to discriminate the two groups was 0.82. 5 The mean plasma concentration of MADDS and the mean plasma acetylation ratio were about three times lower in slow than in rapid acetylators. However, there was no difference in mean plasma DDS concentration between slow and rapid acetylators. 6 There was a significant correlation (r = 0.853, P < 0.001) between plasma MADDS concentration and the acetylation ratio. For DDS such a correlation was absent (r = 0.059, P = 0.23).

The acetylator phenotype was determined in 31 insulin-dependent (IDDM) and 110 noninsulin-dependent (NIDDM) Jordanian diabetics, and was compared to that of 160 healthy volunteers of the same ethnic group. Dapsone was used as the test drug. The rapid acetylator phenotype was slightly less frequent in IDDM and slightly more frequent in NIDDM. Neither of the differences was significant. When acetylator status in the two types of diabetes mellitus was compared, there was a significant difference among the two groups. Patients with IDDM had a higher percentage of the slow acetylator phenotype when compared to NIDDM patients. The association between acetylator status and IDDM in Jordanians, which agrees with that reported for the Saudi Arabian population, is the reverse of what is found in European populations. The results demonstrate ethnic differences in acetylator status among IDDM patients.

The concentrations of dextromethorphan (DM) and its metabolites dextrorphan (DRP), 3-methoxymorphinan (MM) and 3-hydroxymorphinan (HM) were measured in 8 h urine samples from 266 unrelated healthy Jordanian subjects following oral administration of 30 mg dextromethorphan hydrobromide and using a rapid, sensitive and precise HPLC method with fluorometric detection. The frequency of the 'poor' metabolizer status of DM-O-demethylation as judged by log DM/DRP was found to be 6.8% with a 95% confidence interval of 3.8-9.8%. There was a strong correlation between log DM/DRP and log total non-O-demethylated compounds (NODM)/total O-demethylated metabolites (ODM) metabolic ratios (r = 0.96, P < 0.01). However, one subject with log DM/DRP of 0.05 that classifies him as a poor metabolizer was found to have a log NODM/ODM of -0.73 which is in the range of extensive metabolizer status suggesting the presence of another cytochrome P450 isoenzyme involved in dextromethorphan O-demethylation. Dextromethorphan N-demethylation to 3-methoxymorphinan was detected in 55.3% of individuals. Furthermore, a dissociation between dextromethorphan O-demethylation and debrisoquine (D) 4-hydroxylation has been observed. Among the 116 subjects phenotyped with both dextromethorphan and debrisoquine, 7 were poor metabolizers of both, three were poor metabolizers of debrisoquine and extensive metabolizers of dextromethorphan whilst 4 were poor metabolizers of dextromethorphan and extensive metabolizers of debrisoquine, one of whom was reclassified as an extensive metabolizer of dextromethorphan using log NODM/ODM to characterize dextromethorphan metabolizer status.

The frequency distribution of the 8-h urinary ratio of log metoprolol/alpha-hydroxymetoprolol was assessed in 65 healthy, unrelated Jordanian volunteers. There was no apparent bimodality in the frequency distribution of this ratio among the subjects studied. The frequency of the poor metabolizer phenotype of metoprolol alpha-hydroxylation was 1.5% (one subject). There was a significant correlation (r = 0.61, P < 0.05, n = 39) between the log metoprolol/alpha-hydroxymetoprolol and the log debrisoquine/4-hydroxydebrisoquine ratios. However, the frequency of poor metabolizer status of debrisoquine among the 39 subjects was 7.7% (three subjects). Only one of the poor metabolizer of metoprolol alpha-hydroxylation. These findings indicate that metoprolol alpha-hydroxylation by CYP2D6 represents a poor probe for studying debrisoquine polymorphism in Jordanians.

The O-demethylation of dextromethorphan (DMT) to dextrorphan (DRP) was studied in 241 unrelated, healthy Jordanian volunteers (171 males, 70 females). Urine was collected for 8 h following a single oral dose of DMT bromhydrate 30 mg. A thin-layer chromatographic (TLC) technique was used to identify the metaboliser phenotype. The frequency of the poor metaboliser phenotype was found to be 2.9% (approximate 95% confidence interval 0.8-5.0%). Applying the Hardy-Weinberg Law, the frequency of the recessive autosomal gene controlling poor metabolism was 0.17 (95% confidence interval 0.108-0.232).