Abstract:The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009. The 'Wise List' consistently contained 200 drug substances for treating common diseases. The drugs were selected based on their efficacy, safety, suitability and cost-effectiveness. The 'Wise List' was known among one-third of a surveyed sample of the public in 2002 after initial marketing campaigns. All surveyed prescribers knew about the concept and 81% found the recommendations trustworthy in 2005. Adherence to recommendations increased from 69% in 1999 to 77% in 2009. In primary care, adherence increased from 83% to 87% from 2003 to 2009. The coefficient of variation (CV%) decreased from 6.1% to 3.8% for 156 healthcare centres between these years. The acceptance of the 'Wise List' in terms of trust among physicians and among the public and increased adherence may be explained by clear criteria for drug recommendations, a comprehensive communication strategy, electronic access to recommendations, continuous medical education and involvement of professional networks and patients.

Summary:Purpose: To investigate the pharmacokinetics of lamotrigine (LTG) during delivery, during the neonatal period, and lactation.Methods: High-performance liquid chromatography was used to determine plasma and milk levels of LTG in nine pregnant women with epilepsy treated with LTG, and plasma levels in their 10 infants. Samples were obtained at delivery, the first 3 days postpartum, and at breast-feeding 2-3 weeks after delivery.Results: At delivery, maternal plasma LTG concentrations were similar to those from the umbilical cord, indicating extensive placenlal transfer of LTG. There was a slow decline in the LTG plasma concentration in the newborn. At 72 h postpartum, median LTG plasma levels in the infants were 75% of the cord plasma levels (range, 50-100%). The median milk/ maternal plasma concentration ratio was 0.61 (range, 0.47-0.77) 2-3 weeks after delivery, and the nursed infants maintained LTG plasma concentrations of -30% (median, range 23-50%) of the mother's plasma levels. Maternal plasma LTG concentrations increased significantly during the first 2 weeks after parturition, the median increase in plasma concentration/ dose ratio being 170%.Conclusions: Our data demonstrate a marked change in maternal LTG kinetics after delivery, possibly reflecting a normalization of an induced metabolism of LTG during pregnancy. LTG is excreted in considerable amounts in breast milk (the dose to the infant can be estimated to 20.2-1 mg/kg/day 2-3 weeks postpartum), which in combination with a slow elimination in the infants, may result in LTG plasma concentrations comparable to what is reported during active LTG therapy. No adverse effects were observed in the infants, however. Key Words: Epilepsy-Pregnancy-LamotriginePharmacokinetics-Breast milk.Lamotrigine (LTG) is a widely used antiepileptic drug (AED) currently available in -70 countries. With a more widespread use of the drug, an increasing number of women will be exposed to LTG during pregnancy and lactation. An International Lamotrigine Pregnancy Registry has been set up by the manufacturer to collect information about pregnant women exposed to LTG (1). As of March 31, 1999, 167 pregnancies with LTG exposure had been prospectively included. The registry is focusing on pregnancy outcome in terms of birth defects. However, most women who take AEDs during pregnancy continue to do so after delivery. The drugs may thus affect the child, not only in the form of birth defects induced in early fetal life, but also through pharmacologic effects later in pregnancy, after delivery, and during lactation. It is for this reason important to obtain Accepted January 26, 2000. Address correspondence and reprint requests to Dr. I. Ohman at Department of Clinical Pharmacology, Karolinska Hospital, S-171 76 Stockholm, Sweden, E-mai1:inoeh 63 mb.ks.se information on transfer of the drug over the placenta, on the capacity of the newborn to eliminate the drug, and on the exposure of the infant to the drug through breastfeeding.LTG is a phenyltriazine AED structurally unrelated...

The plasma concentration of the atherogenic low density lipoproteins (LDL) increases with age. To clarify the mechanism of this change, we studied the kinetics of autologous '25I-LDL apolipoprotein B (apo B) in 41 normolipidemic, nonobese healthy males. For comparison, they were divided into three age groups: young, 21-39 yr (n = 18), middle-aged, 40-59 yr (n = 11), and old, 60-80 yr (n = 12). The levels of plasma LDL cholesterol and LDL apo B increased from respectively 3.4±0.1 (SEM) mmol/liter and 86±2 mg/dl in the young to 4.1±0.1 mmol/liter and 95±3 mg/dl in the old (P < 0.01), and this increase was linked to a progressively decreased (r = -0.38, P < 0.02) fractional catabolic rate of LDL apo B (0.348±0.010 pools per day in the young vs. 0.296±0.009 pools per day in the old, P < 0.01). The production rate of LDL apo B did not differ significantly between the groups. The reduced fractional catabolic rate of LDL apo B in the old was not associated with a decrease in binding affinity of the LDL particle to its receptor, as judged from its ability to compete for '"I-LDL fibroblast binding. When hepatic LDL receptor expression was stimulated by cholestyramine treatment in six old males, their LDL apo B fractional catabolic rate increased to the levels observed in the young subjects. We conclude that the increase in LDL which normally occurs with age is explained by a reduced capacity for its removal, and hypothesize that this is mediated via a reduced hepatic LDL receptor expression. (J. Clin. Invest. 1991. 87:591-596.).

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