Can chronic maternal drug therapy alter the nursing infant's hepatic drug metabolizing enzyme pattern?
This study was carried out to investigate whether minute quantities of maternal drugs ingested over an extended period of time by a breast-feeding infant can alter the activity pattern of the infant's hepatic drug metabolizing enzyme (HDME). The HDME activity patterns of 12 breast-fed infants whose mothers were not on drug therapy were compared with those of 11 infants whose mothers had been taking 30 micrograms levo-norgesterel daily for 90 to 195 days (oral contraceptives group) and of 10 infants whose mothers had been taking ethambutol and isoniazid daily since pregnancy (tuberculosis group). As 6 beta hydroxycortisol in urine is considered to be a good and acceptable reflector of HDME activity, it was estimated from the infants' urine using enzyme-linked immunosorbent assay (ELISA) technique. A comparison of the patterns between 90 days of age and 195 days of age of the infants in the control group and the two study groups indicated an increase from 36.6 ng/mL to 58.4 ng/mL at 195 days in the control group. An initial decrease from 36.6 ng/mL to 26.2 ng/mL was noted with commencement of maternal levo-norgesterel therapy, followed by a slow and steady rise to 47.8 ng/mL at 195 days of age, with a shift in the peak from 120 to 135 days of infants age in the oral contraceptive group. A suppressed pattern with decreased levels of 6 beta hydroxycortisol ranging from 19.3 ng/mL to 26.5 ng/mL at 195 days was found in the tuberculosis group. The data were analyzed by two-way analysis of variance (ANOVA) coupled with Duncan's Multiple range test. Both treatment group showed significant differences from the control group at the 0.050 level. The HDME plays an important role in determining the final outcome of any drug in humans, as it controls the metabolism of drugs. Hence, alterations in its activity caused by the transfer of maternal drugs over a prolonged period of time could pose a serious problem to nurslings when they require drugs for their own benefit.
Toddywalla
V S
VS
Metabolic Unit, Institute for Research in Reproduction, Indian Council of Medical Research, Bombay, India.
Patel
S B
SB
Betrabet
S S
SS
Kulkarni
R D
RD
Kombo
I
I
Saxena
B N
BN
D000328:Adult; D001942:Breast Feeding; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D007223:Infant; D007231:Infant, Newborn; D016912:Levonorgestrel / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008895:Milk, Human / Q000378:metabolism*; D011247:Pregnancy
D016912:Levonorgestrel; D006854:Hydrocortisone