Clomipramine concentration and withdrawal symptoms in 10 neonates.

AIM: After in utero exposure to tricyclic antidepressants, neonatal withdrawal symptoms have been reported with an estimated incidence between 20 and 50%; however, few data are available for clomipramine. This could also be the case for neonatal pharmacokinetic clomipramine parameters and so this study was set up. METHODS: Babies exposed to clomipramine in utero were included in an observational study, approved by the local ethics committee, after written informed consent. Withdrawal symptoms were scored at 12, 24 and 48 h after birth using the Finnegan score. Plasma concentrations were determined using an in-house-developed, validated liquid chromatography with mass detection (LC-MSMS) method at 0, 12, 24 and 48 h after birth. RESULTS: We found that three of 11 pregnancies were complicated with pre-eclampsia. Ten neonates were observed for clomipramine withdrawal symptoms. The observed withdrawal symptoms were too short a period of sleep after feeding (6), poor feeding (3), mild to severe tremors (6), hyperactive Moro reflex (3) and respiratory rate >60 breaths min(-1). Serious withdrawal reactions, such as tachycardia and cyanosis, were seen. We calculated a half-life value of 42 ± 16 h for clomipramine in neonates. Only a weak correlation was found between withdrawal reactions and clomipramine plasma concentration or desmethylclomipramine plasma concentration. CONCLUSIONS: In neonates, clomipramine is eliminated with a half-life value of 42 h, compared with 20 h in adults. In two of 10 neonates, tachycardia and cyanosis were seen as serious withdrawal symptoms after maternal use of clomipramine.

Influence of bariatric surgery on the use and pharmacokinetics of some major drug classes.

The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes to be searched for were antidepressants, antidiabetics, statins, antihypertensive agents, corticosteroids, oral contraceptives, and thyroid drugs. A reduction in the use of medication by patients after bariatric surgery has been reported for various drug classes. Very few studies have been published on the influence of bariatric surgery on the pharmacokinetics of drugs. After bariatric surgery, theoretically, reduced drug absorption may occur. Correct dosing and choosing the right dosage form for drugs used by patients after bariatric surgery are necessary for optimal pharmacotherapy. Therefore, more clinical studies are needed on the influence of bariatric surgery on the pharmacokinetics of major drugs.

Cannabinoids in oral fluid following passive exposure to marijuana smoke.

The concentration of tetrahydrocannabinol (THC) and its main metabolite 11-nor-Δ(9)-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) as well as cannabinol (CBN), and cannabidiol (CBD) were measured in oral fluid following realistic exposure to marijuana in a Dutch coffee-shop. Ten healthy subjects, who were not marijuana smokers, volunteered to spend 3h in two different coffee shops in Groningen, The Netherlands. Subjects gave two oral fluid specimens at each time point: before entering the store, after 20 min, 40 min, 1h, 2h, and 3h of exposure. The specimens were collected outside the shop. Volunteers left the shop completely after 3h and also provided specimens approximately 12-22 h after beginning the exposure. The oral fluid specimens were subjected to immunoassay screening; confirmation for THC, cannabinol and cannabidiol using GC/MS; and THC-COOH using two-dimensional GC-GC/MS. THC was detectable in all oral fluid specimens taken 3h after exposure to smoke from recreationally used marijuana. In 50% of the volunteers, the concentration at the 3h time-point exceeded 4 ng/mL of THC, which is the current recommended cut-off concentration for immunoassay screening; the concentration of THC in 70% of the oral fluid specimens exceeded 2 ng/mL, currently proposed as the confirmatory cut-off concentration. THC-COOH was not detected in any specimens from passively exposed individuals. Therefore it is recommended that in order to avoid false positive oral fluid results assigned to marijuana use, by analyzing for only THC, the metabolite THC-COOH should also be monitored.