Can Chronic Maternal Drug Therapy Alter the Nursing Infant's Hepatic Drug Metabolizing Enzyme Pattern?

Abstract

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.

Transfer of isoniazid from circulation to breast milk in lactating women on chronic therapy for tuberculosis

“…The previous finding by Toddywalla et al. [12] also suggests that isoniazid is able to suppress infant hepatic metabolizing capacity. Thus, while studying the presence of drugs in milk, not only should the drug characteristics and maternal factors be considered, but also the infant's capability to metabolize the drugs should not be ignored.…”

“…Toddywalla et al. have reported that isoniazid is capable of suppressing hepatic drug metabolizing activity (HDME) in nurslings of mothers on therapy [12]. It is therefore important to assess the extent of exposure of these infants to the drug through breast milk, so as to avoid over‐exposure and its adverse effects.…”

Development of an in vitro cell culture model to study milk to plasma ratios of therapeutic drugs

“…It is well established that almost all drugs taken by nursing mothers pass into breast milk in a “pharmacologically active” form,[12] thereby, exposing the nursling to these pharmacologically active drugs. This exposure could be potentially harmful as it occurs during the nursling's rapid growth and development phase, when its drug metabolizing and excretory systems are still immature.…”

Severe neutropenia in a breastfed infant: a case report and discussion of the differential diagnosis

“…Although concentrations are low and toxic concentrations are rarely reached, pharmacological activity is possible. 14 Toddywalla et al 19 reported that INH is capable of suppressing hepatic drug metabolizing activity in infants of mothers on chronic therapy, and Pariente-Khayat et al 20 reported that the maturation of N-acetyltransferase 2, which is the main route of metabolizing INH, 14 occurs in the first 4 years of life. 14 , 17 , 20 …”