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.

1 Plasma concentrations of pentamidine were measured up to 1-8 months after a single 2 h i.v. infusion of 3.0 to 4.8 mg kg-1 pentamidine isethionate in 11 patients with late stage Trypanosoma gambiense sleeping sickness. 2 Maximum plasma drug concentrations varied between 713 and 2461 nmol 1-1.After termination of infusion, a rapid distribution phase over 10 min was followed by a slower distribution phase and an elimination phase prolonged over weeks to months. 3 The 'terminal'"elimination rate constant could be determined in six patients and subsequent kinetic calculations showed a three to fourfold variation in plasma clearance and 'terminal' half-life (median 1126 (range 553-2036) ml min-1 and 265 (107-446) h, respectively). The median apparent volume of distribution (Vss) was 11 850 1. Renal clearance accounted for a median of 11% of total plasma clearance, indicating that metabolism is a major route of pentamidine elimination in man. 4 Side effects were few and mild and a slight or moderate decrease in blood pressure was the most common registered adverse reaction observed in four subjects. 5 The prolonged elimination of pentamidine seems inconsistent with the present recommended dosage regimen of pentamidine for treatment of trypanosomiasis of 7 to 10 parenteral doses given once daily or every second day.

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Objective-To assess the diagnostic value and safety of the benzodiazepine antagonist flumazenil in patients with coma ofunclear origin with suspected poisoning.Design-Double blind, placebo controlled, randomised study.Setting-Intensive care unit at a major teaching hospital.Patients-105 Unconscious adults admitted consecutively with suspected drug overdosage during 18 months from a total of 362 cases of poisoning. Exclusion criteria were pregnancy, epilepsy, obvious poisoning with drugs identified unequivocally from information from relatives or others as other than benzodiazepines, and coma score >10 on a scale graded from 4 to 20. Patients were allocated randomly to receive flumazenil (21 men and 32 women) or placebo (25 men and 27 women).Interventions -Intravenous injection offlumazenil (10 ml, 0-1 mg/ml) or placebo (10 ml vehicle alone) given double blind over three minutes.Main outcome measures -Serum and urine concentrations ofbenzodiazepines, antidepressants, and several other agents; blood gas tensions; standardised evaluation on admission and five minutes after the injection by means of coma scale score and urgent diagnostic or therapeutic interventions indicated according to the history and clinical examination; standardised interview after the injection to try to ascertain further information; and adverse reactions.Results-Benzodiazepines were found in the serum in 36 of the 53 patients in the flumazenil group and in 37 of the 52 who received placebo. The average coma scale score increased significantly after injection in the flumazenil group (6-4 v 12-1, p<0-001) but not in the placebo group. In the flumazenil group several interventions were rendered unnecessary by the injection: gastric lavage and urinary catheterisation (19 patients each), intubation (21), artificial ventilation and computed tomography of the brain (three patients each), blood culture and lumbar puncture (one patient each), and electroencephalography (two). In the placebo group the indications for these procedures did not change in any patient after injection. The 95% confidence interval for the difference in reduction of the frequency ofindications for gastric lavage after injection between the two groups was 21% to 51%, that for intubation 25% to 55%, and that for urinary catheterisation 21% to 51%. In the flumazenil group 21 patients gave valuable information on their drug ingestion within 10 minutes after injection compared with only one in the placebo group (p<0-001). Nine adverse reactions were recorded in the flumazenil group, eight of which were graded as mild and one severe.