Both genetic and non-genetic factors were found to influence lamotrigine pharmacokinetics. These factors should be considered when determining lamotrigine dosing. The model presented here could be useful for lamotrigine dose adjustment in clinical practice.

Therapeutic drug monitoring (TDM) may be beneficial when applied to antiretroviral (ARV). Even though TDM can be a valuable strategy in HIV management, its role remains controversial. Areas covered: This review provides a comprehensive update on important issues relating to TDM of ARV drugs in HIV-infected patients. Articles from PubMed with keywords relevant to each topic section were reviewed. Search strategies limited to articles published in English. Expert commentary: There is evidence supporting the use of TDM in HIV treatment. However, some limitations need to be considered. The evidence supporting the use of routine TDM for all patients is limited, as it is not clear that this strategy offers any advantages over TDM for selected indications. Selected groups of patients including patients with physiological changes, patients with drug-drug interactions or toxicity, and the elderly could potentially benefit from TDM, as optimized dosing is challenging in these populations.

Lamotrigine is being used more frequently in elderly patients. Dosing of lamotrigine in elderly patients is based largely on studies from younger adults and not evidence-based data from elderly patients. The goal of this study is to determine the pharmacokinetic parameters, such as clearance, and the factors that have a significant effect on these parameters to provide evidence-based information that can be used to dose elderly patients taking lamotrigine. Lamotrigine plasma concentrations from 148 elderly patients (aged 59-92 years) were used to develop a population pharmacokinetic model. Data were analyzed using NONMEM. Model evaluation was performed using the bootstrap approach and predictive check. The results showed that the blood urea nitrogen/serum creatinine ratio, weight, and phenytoin use significantly affect apparent clearance of lamotrigine. These results show that clinicians may need to take into account these covariates when dosing lamotrigine in this population.

f Tenofovir (TFV) is eliminated by renal excretion, which is mediated through multidrug-resistant protein 2 (MRP2) and MRP4, encoded by ABCC2 and ABCC4, respectively. Genetic polymorphisms of these transporters may affect the plasma concentrations of tenofovir. Therefore, the aim of this study was to investigate the influence of genetic and nongenetic factors on tenofovir plasma concentrations. A cross-sectional study was performed in Thai HIV-infected patients aged >18 years who had been receiving tenofovir disoproxil fumarate at 300 mg once daily for at least 6 months. A middose tenofovir plasma concentration was obtained. Multivariate analysis was performed to investigate whether there was an association between tenofovir plasma concentrations and demographic data, including age, sex, body weight, estimated glomerular filtration rate (eGFR), hepatitis B virus coinfection, hepatitis C virus coinfection, duration of tenofovir treatment, concomitant use of ritonavir-boosted protease inhibitors, and polymorphisms of ABCC2 and ABCC4. A total of 150 Thai HIV-infected patients were included. The mean age of the patients was 43.9 ؎ 7.2 years. The mean tenofovir plasma concentration was 100.3 ؎ 52.7 ng/ml. In multivariate analysis, a low body weight, a low eGFR, the concomitant use of ritonavir-boosted protease inhibitors, and the ABCC4 4131T ¡ G variation (genotype TG or GG) were independently associated with higher tenofovir plasma concentrations. After adjusting for weight, eGFR, and the concomitant use of ritonavir-boosted protease inhibitors, a 30% increase in the mean tenofovir plasma concentration was observed in patients having the ABCC4 4131 TG or GG genotype. Both genetic and nongenetic factors affect tenofovir plasma concentrations. These factors should be considered when adjusting tenofovir dosage regimens to ensure the efficacy and safety of a drug. (This study has been registered at ClinicalTrials.gov under registration no. NCT01138241.) T enofovir disoproxil fumarate (TDF), an oral prodrug of tenofovir (TFV), is widely used for the treatment of human immunodeficiency virus (HIV) infection because of its high potency, good safety profile, limited drug interaction, and convenient once-daily dosing (1, 2). After absorption, TDF is rapidly converted to tenofovir. Tenofovir is then phosphorylated intracellularly to tenofovir diphosphate, an active analog, which inhibits HIV reverse transcriptase, resulting in a termination DNA chain elongation (1, 2).Tenofovir is eliminated by renal excretion through glomerular filtration and active tubular secretion. It is transported into kidney tubular cells by organic anion transporter 1 (OAT1) and OAT3, encoded by the SLC22A6 and SLC22A8 genes, respectively, at the basolateral membrane. Subsequently, tenofovir is secreted to the tubular lumen by multidrug-resistant protein 2 (MRP2) and MRP4, encoded by the ABCC2 and ABCC4 genes, respectively, at the apical membrane (3). Therefore, genetic polymorphisms of these transporter genes may affect the transport of tenofovir at ...

Background and objective-Carbamazepine is a potent inducer of drug metabolizing enzymes, which results in a number of clinically significant drug-drug interactions. Deinduction occurs when chronic carbamazepine therapy is discontinued. The goal of this study was to develop a population pharmacokinetic model to describe the time course of carbamazepine deinduction.