Usefulness of vancomycin treatment individualization via Bayesian algorithms: a 5-year study in critical patients.

Compare two vancomycin dosing strategies in critical patients with methicillin-resistant (MRSA) infections, considering the heterogeneity of the dosing regimens administered and their implications for toxicity and efficacy. Longitudinal retrospective observational study in two patient cohorts (standard dosing vs dosing via Bayesian algorithms). The group of Bayesian algorithms received substantially higher and significantly heterogeneous doses, with an absence of nephrotoxicity.

Individualized Protease Inhibitor Monotherapy: The Role of Pharmacokinetics and Pharmacogenetics in an Aged and Heavily Treated HIV-Infected Patient.

Antiretroviral therapy has changed the history of HIV infection from a lethal disease to a chronic infection, with the emergence of long-term adverse effects. Herein we present a case of a heavily treated HIV-infected man in whom antiretroviral toxicity had been observed. The lopinavir/ritonavir plasma concentrations at standard doses were significantly above the recommended levels.

Gene-gene interactions between DRD3, MRP4 and CYP2B6 polymorphisms and its influence on the pharmacokinetic parameters of efavirenz in HIV infected patients.

Genetic factors have a significant impact on the PK variability of EFV, much higher than other non-genetic factors, such as demography. In this work we have performed a comprehensive PG analysis of genes encoding the major metabolizing enzymes and transporters of EFV, establishing a clear relationship between the PK parameters and genetic factors, which explain 50% of the variability in EFV PK parameters. The most relevant associations for metabolizing enzymes were found in CYP2B6 (rs3745274), in agreement with previous studies.

A pharmacist's role in the individualization of treatment of HIV patients.

The pharmacological treatment of HIV is complex and varies considerably among patients, as does the response of patients to therapy, requiring treatment plans that are closely tailored to individual needs. Pharmacists can take an active role in individualizing care by employing their knowledge of pharmacokinetics and pharmacogenetics and by interacting directly with patients in counseling sessions. These strategies promote the following: maintenance of plasma concentrations of antiretroviral agents within therapeutic ranges, prediction of pharmacological response of patients with certain genetic characteristics, and clinical control of HIV through the correct use of antiretroviral treatments.

CYP3A4 polymorphism and lopinavir toxicity in an HIV-infected pregnant woman.

Cytochrome P450 (CYP) 3A4 has been considered to be the most important enzyme system for metabolism of lopinavir/ritonavir (LPV/r), a widely used HIV protease inhibitor (PI) recommended during pregnancy. Herein we present a clinical case of a pregnant HIV-infected woman who was taking standard doses of LPV/r, 400/100 mg twice daily. The trough plasma concentrations for LPV were fourfold above that recommended for PI-pretreated patients and toxicity associated with LPV/r and PI regimens was observed.

Population pharmacokinetic/pharmacogenetic model of lopinavir/ritonavir in HIV-infected patients.

Aim: This study aims to develop a population pharmacokinetic/pharmacogenetic model for lopinavir/ritonavir (LPV/r) in European HIV-infected patients.

Materials & Methods: A total of 693 LPV/r plasma concentrations were assessed and 15 single-nucleotide polymorphisms were genotyped. The population pharmacokinetic/pharmacogenetic model was created using a nonlinear mixed-effect approach (NONMEM v.

Dose reduction of efavirenz: an observational study describing cost-effectiveness, pharmacokinetics and pharmacogenetics.

Aim: Antiretroviral treatment implies a high cost to the healthcare system. The aim of this study was to evaluate the clinical and economic impact of efavirenz (EFV) dose adjustment by monitoring plasma concentrations and pharmacogenetic analysis of the 516G>T CYP2B6 polymorphism.

Materials & Methods: One hundred and ninety HIV patients treated with EFV were studied.

Toxicogenetics of lopinavir/ritonavir in HIV-infected European patients.

Aims: We present a genetic association study in 106 European HIV-infected individuals aimed at identifying and confirming polymorphisms that have a significant influence on toxicity derived from treatment with lopinavir/ritonavir (LPV/r).

Patients & Methods: Genotyping was performed by matrix-assisted laser desorption/ionization-time of flight and KASPar (KBiosciences, Hoddesdon, UK); LPV/r plasma concentrations were quantified using HPLC with an UV detection system and the pharmacokinetic parameters were estimated using Bayesian algorithms. Genetic association analysis was performed with PASW Statistics 18 (SPSS Inc.

Impact of a pharmaceutical care program on clinical evolution and antiretroviral treatment adherence: a 5-year study.

Background: Antiretroviral treatments (ART) form the basis of adequate clinical control in human immunodeficiency virus-infected patients, and adherence plays a primary role in the grade and duration of the antiviral response. The objectives of this study are: (1) to determine the impact of the implementation of a pharmaceutical care program on improvement of ART adherence and on the immunovirological response of the patients; and (2) to detect possible correlations between different adherence evaluation measurements.

Methods: A 60-month long retrospective study was conducted.

Impact of pharmacogenetics on CNS side effects related to efavirenz.

Aim: This article evaluates which genetic factors are involved in CNS toxicity related to long-term treatment with efavirenz (EFV) standard doses and their relationship with plasma concentrations.

Patients & Methods: A total of 119 HIV-positive patients, in which 1350 EFV plasma concentrations, 68 SNPs and 14 EFV-related adverse effects (AEs) were analyzed.

Results: Overall, 32.

[New strategies in the optimisation of lopinavir/ritonavir doses in human immunodeficiency virus-infected patients].

Lopinavir/ritonavir (LPV/r) has demonstrated virological and immunological efficacy in the combined antiretroviral treatment (cART), in both naïve and experienced patients. Furthermore, LPV/r showed a high barrier to the development of resistance. Although generally well tolerated, adverse gastrointestinal side effects and metabolic disorders are frequent.

The convergence of therapeutic drug monitoring and pharmacogenetic testing to optimize efavirenz therapy.

The aim of this study was to show the benefits of combining therapeutic drug monitoring (TDM) and pharmacogenetic analyses to optimize efavirenz (EFV) therapy. Patients were selected to minimize nongenetic differences between patients: 32 HIV adherent patients without drug interactions treated with an EFV nonindividualized dose over at least 1 year and included in a TDM program were genotyped according to minimum steady-state concentrations (C ss min). The EFV plasma concentrations (n = 158) were quantified by high-performance liquid chromatography-ultraviolet, and genetic polymorphisms were analyzed using the PHARMAchip.

Long-term efficacy and safety of efavirenz dose reduction to 200 mg once daily in a Caucasian patient with HIV.

A 48-year-old Caucasian male patient presented with severe adverse drug events (ADEs) while being treated with a standard dose (600 mg/day) of efavirenz. The patient's clinical course was favourable; however, he also described intense nightmares, cramps in his legs and anxiety disturbances that made him highly irritable. Measurement of the patient's efavirenz plasma concentrations revealed a mean minimum steady-state concentration during a dosage interval (C(min,ss)) of 12.