Transfer of buprenorphine into breast milk and calculation of infant drug dose.

Little is known about the safety of buprenorphine (BUP) in breastfeeding. The aim of this work was to investigate the transfer of buprenorphine and its main active metabolite, norbuprenorphine (n-BUP), into human milk and to determine the drug dose and effects in exposed infants. Seven lactating women, who were maintained on BUP treatment because of previous opiate addiction, were studied in an open observational study. All mothers had a strong wish to breastfeed their newborn infants. Buprenorphine samples for analysis were collected from the urine of 6 infants together with breast milk, blood, and urine from their mothers during a 24-hour period in the week after birth. One mother-infant pair was studied at 9 months of age. Buprenorphine and n-BUP were analyzed by a liquid chromatography/mass spectrometry method suitable for handling different matrices. Buprenorphine and n-BUP were found in low levels in the infants' urine. Breastfed infants were exposed to a calculated BUP dose per kg bodyweight less than 1%, with an average milk/plasma area under the curve of 1.7 (range, 1.1-2.8) for BUP and 0.7 (range, 0.4-1.2) for n-BUP. These data support the use of BUP during breastfeeding. However, the authors recommend that infants be monitored closely.

The African-specific CYP2D617 allele encodes an enzyme with changed substrate specificity.

OBJECTIVE: The effects of the CYP2D6*17 and *29 alleles on substrate specificity and enzyme activity were studied by correlating CYP2D6 genotype to phenotype with 4 probe drugs (codeine, debrisoquine, dextromethorphan, metoprolol) in black Tanzanians and white Swedes. METHODS: The black Tanzanian subjects represented the following 6 genotypic groups: A, (CYP2D6*1 or *2)/(*1 or *2) (n = 13); B, CYP2D6*17 /*17 (n = 5); C, CYP2D6*29 /*29 (n = 4); D, CYP2D6*1 /*17 (n = 5); E, CYP2D6*5/*17 (n = 4); and F, various genotypes (n = 4). The white subjects were from 4 groups, as follows: A, (CYP2D6*1 or *2)/(*1 or *2) (n = 7); B, (CYP2D6*1 or *2)/(*3, *4, or *5) (n = 7); C, homozygous for defect alleles (n = 7); and D, duplicated CYP2D6 gene (n = 2). RESULTS: The metabolic ratios of the 4 probe drugs correlated significantly (r (s) = 0.69-0.92; P <.001) in both populations. Tanzanian subjects homozygous for the CYP2D6*17 allele were slower metabolizers when debrisoquine or dextromethorphan was used as the probe drug than when codeine or metoprolol was used, showing a different substrate specificity of CYP2D6.17 than of CYP2D6.1 and CYP2D6.2. This was confirmed with analysis of covariance of the different metabolic ratios for a subgroup of subjects carrying only the CYP2D6*17 mutated allele (n = 9) compared with all other subjects (n = 44). The metabolic ratios of dextromethorphan and metoprolol differed significantly among Tanzanian subjects homozygous for the CYP2D6*29 allele compared with those with CYP2D6*1 or *2 alleles. CONCLUSION: We found differences in the disposition of 4 CYP2D6 probe drugs in black Tanzanians compared with Swedes. The differences were caused by the presence of CYP2D6.17 and CYP2D6.29. The results show that CYP2D6.17 exhibits altered substrate specificity compared with CYP2D6.1 and CYP2D6.2.