1 Chloroquine was given in 300 mg single doses as an i.v. infusion, an oral solution and as tablets at intervals of at least 56 days to 11 healthy volunteers. Concentrations of chloroquine and its metabolite desethylchloroquine were measured in plasma, erythrocytes and urine using h.p.l.c.
A retrospective study covering a 14-year period was carried out to estimate the incidence and assess the clinical features of benzodiazepine (BZD) poisoning. The annual contribution of BZDs to the total number of drug overdose cases admitted to an intensive care unit displayed an increasing trend over the period, and during the last years BZDs were involved in nearly one-third of all cases. Among the 702 cases of BZD overdosage, 144 had ingested BZD alone, 200 had poisoned themselves with BZD combined with alcohol and 358 had taken BZD with other miscellaneous drugs. In 56% of all the cases the patients had severe central nervous system depression on admission. In 47% orotracheal intubation was performed and in 18% artificial ventilation was administered. Complications were recorded in 69 of the 702 cases (9.8%) and five cases were fatal. These clinical features were essentially the same in the group that had overdosed with just BZD. In conclusion, patients with drug overdosage involving BZD have a low hospital mortality, but the acute somatic risk is not negligible. Moreover, they consume a substantial proportion of the resources in the emergency room and the intensive care unit.
Chloroquine protein binding was determined by equilibrium dialysis of purified plasma proteins and plasma samples from 20 healthy subjects and 14 patients with rheumatoid arthritis. The mean binding was 61 + 9% in plasma from healthy subjects (range 46-74%) and 64 + 7% in plasma from rheumatoid arthritis patients (range 55-79%). Albumin and a,-acid glycoprotein at physiological concentrations bound chloroquine to an approximately equal extent. Protein binding is unlikely to be an important determinant of chloroquine pharmacokinetics or response.
This small, clinical cohort showed no significant association between mothers' prenatal exposure to lithium or mood disorders and their offspring's IQ.
Purpose
Sertraline, a selective serotonin reuptake inhibitor (SSRI), is one of the most commonly used antidepressant during pregnancy. Plasma sertraline concentrations vary markedly between individuals, partly explained by variability in hepatic drug metabolizing cytochrome P450-enzyme activity. Our purpose was to study the variability in the plasma concentrations in pregnant women and the passage to their infants.
Method
Pregnant women with moderate untreated depression were recruited in 2016–2019 in Stockholm Region and randomized to treatment with sertraline or placebo. All received Internet-based cognitive behavior therapy as non-medical treatment. Sertraline plasma concentrations were measured around pregnancy weeks 21 and 30, at delivery, 1-month postpartum, in cord blood and at 48 h of age in the infant. The clinical course of the infants was followed.
Results
Nine mothers and 7 infants were included in the analysis. Median dose-adjusted sertraline concentration in second trimester was 0.15(ng/mL) /(mg/day), in third trimester and at delivery 0.19 and 1-month postpartum 0.25, with a 67% relative difference between second trimester and postpartum. The interindividual variation was 10-fold. Median concentrations in the infants were 33% and 25% of their mothers’, measured in cord blood, and infant plasma, respectively. Only mild and transient adverse effects were seen on the infants.
Conclusion
Placental passage of sertraline to the infant is low. However, the interindividual variation in maternal concentrations during pregnancy is huge, why therapeutic drug monitoring might assist in finding the poor metabolizers at risk for adversity and increase the safety of the treatment.
Trial registration
The trial was registered at clinicaltrials.gov July 9, 2014 with TRN: NCT02185547.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.