Confirming the Suitability of a Gentamicin Dosing Strategy in Neonates Using the Population Pharmacokinetic Approach with Truncated Sampling Duration.

(1) Background: Gentamicin is known to be nephrotoxic and ototoxic. Although gentamicin dosage guidelines have been established for preterm and term neonates, reports do show attainment of recommended peak concentrations but toxic gentamicin concentrations are common in this age group. (2) Methods: This was a prospective, observational study conducted in Namibia with 52 neonates.

Predictors of gentamicin therapy failure in neonates with sepsis.

Sepsis is a common disease with high morbidity and mortality among newborns in intensive care units world-wide. Gram-negative bacillary bacteria are the major source of infection in neonates. Gentamicin is the most widely used aminoglycoside antibiotic in empiric therapy against early-onset sepsis.

Performance of the allometric power model in scaling from adult to paediatric antiretroviral dose in children at a Referral Hospital in Windhoek, Namibia.

Background: World Health Organization (WHO) advocates use of weight bands in antiretroviral therapy (ART) guidelines. Allometric scaling could be a more reliable method because it uses a non-linear approach in relating dose to body weight. This study evaluates performance of the allometric ¾ power model in comparison to WHO weight band method in children receiving ART.

Plasma concentration and eGFR in preterm and term neonates receiving gentamicin or successive amikacin therapy.

Background: Gentamicin and amikacin are aminoglycoside antibiotics which are renally excreted and known to be nephrotoxic. Estimate of glomerular filtration rate (eGFR) per body surface area is lower in neonates than in adults and exposure to these drugs could lead to more suppression in kidney function. The aim of this study was to determine maximum and minimum plasma concentrations (C and C), time to reach C levels of gentamicin and amikacin, and to assess eGFR in preterm and term neonates.

Therapeutic drug monitoring of phenytoin and valproic acid in critically ill patients at Windhoek Central Hospital, Namibia.

Background: Phenytoin and valproic acid, anticonvulsants, have a low therapeutic index and are highly plasma protein bound, mainly to albumin. Hypoalbuminaemia is common in critically ill patients and increases the unbound drug concentration. Thus, monitoring unbound rather than total plasma drug concentrations is recommended to optimise the dosing of these drugs.

Should Codeine Still be Considered a WHO Essential Medicine?

Codeine continues to be widely used as an analgesic, antidiarrhoeal and antitussive agent. Its analgesic effect depends on its biotransformation to morphine, a strong opioid. The highly variable biotransformation of codeine to morphine, catalysed by CYP2D6, underlies the pronounced interindividual variability of its analgesic response.

Predictors of loss to follow-up of tuberculosis cases under the DOTS programme in Namibia.

Background: In Namibia, one out of every 25 cases of tuberculosis (TB) is "lost to follow-up" (LTFU). This has impacted negatively on national efforts to end the disease by 2035. The aim of this study was to determine the trends and predictors of LTFU under the directly observed treatment short-course (DOTS) programme in Namibia.

Predictors of tuberculosis treatment success under the DOTS program in Namibia.

Objectives: Optimal treatment success rates are critical to end tuberculosis in Namibia. Despite the scale-up of high quality directly observed therapy short-course strategy (DOTS) in Namibia, treatment success falls short of the global target of 90%. The objective of this study was to ascertain the predictors of treatment success rates under DOTS in Namibia to provide future direction.

Monitoring of gentamicin serum concentrations in obstetrics and gynaecology patients in Namibia.

Background Therapeutic drug monitoring is frequently used to optimize the gentamicin dose. Objective The study investigated whether a 240 mg once daily standard dose achieves the recommended target serum gentamicin concentrations. Setting The prospective, observational study took place in the 2 major public hospitals in Namibia.

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril.

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the marketing authorization of immediate-release, solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed from the gastrointestinal tract into the enterocytes.

Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring.

Introduction: Tuberculosis (TB) remains one of the world's deadliest communicable diseases. Although cure rates of the standard four-drug (rifampicin, isoniazid, pyrazinamide, ethambutol) treatment schedule can be as high as 95-98 % under clinical trial conditions, success rates may be much lower in less well resourced countries. Unsuccessful treatment with these first-line anti-TB drugs may lead to the development of multidrug resistant and extensively drug resistant TB.

The Lidose hard capsule formulation of fenofibrate is suprabioavailable compared to the nanoparticle tablet formulation under high-fat fed conditions.

Purpose: The therapeutic equivalence of multiple registered fenofibrate formulations, several of which are suprabioavailable and therefore marketed at lower dosage strengths than their reference products, is based on the results of bioequivalence studies. Most of these formulations show a higher bioavailability when taken with a high-fat meal. The relative bioavailability of two of these formulations, the 200 mg Lidose hard capsules and the 145 mg nanoparticle tablets, was assessed when taken with a high-fat meal.

Prediction of paraquat exposure and toxicity in clinically ill poisoned patients: a model based approach.

Aims: Paraquat poisoning is a medical problem in many parts of Asia and the Pacific. The mortality rate is extremely high as there is no effective treatment. We analyzed data collected during an ongoing cohort study on self-poisoning and from a randomized controlled trial assessing the efficacy of immunosuppressive therapy in hospitalized paraquat-intoxicated patients.

Population pharmacokinetic analysis of tacrolimus early after pediatric liver transplantation.

Background: Tacrolimus (TAC) pharmacokinetics (PKs) show considerable unexplained variability, particularly in the early period after transplantation. Therefore, TAC is a good candidate for therapeutic drug monitoring. The main objective of the present work was to propose a robust PK model for TAC in the early period after transplantation, with the final goal to provide practitioners with a tool for dose individualization in pediatric patients.

The revised EMA guideline for the investigation of bioequivalence for immediate release oral formulations with systemic action.

On August 1, 2010, a revised guidance regarding bioequivalence (BE) assessment for the approval of innovator (bridging studies, variations, line extensions) and generic medicinal products in the EU came into effect (EMA Guideline on the Investigation of Bioequivalence, CPMP/EWP/QWP/1401/98 Rev. 1/Corr**, London, 20 January 2010). This guideline specifies the requirements for BE assessment for immediate release oral dosage forms with systemic action.

Statistical tools for dose individualization of mycophenolic acid and tacrolimus co-administered during the first month after renal transplantation.

Aim: To predict simultaneously the area under the concentration-time curve during one dosing interval [AUC(0,12 h)] for mycophenolic acid (MPA) and tacrolimus (TAC), when concomitantly used during the first month after transplantation, based on common blood samples.

Methods: Data were from two different sources, real patient pharmacokinetic (PK) profiles from 65 renal transplant recipients and 9000 PK profiles simulated from previously published models on MPA or TAC in the first month after transplantation. Multiple linear regression (MLR) and Bayesian estimation using optimal samples were performed to predict MPA and TAC AUC(0,12 h) based on two concentrations.

Population pharmacokinetics of four β-lactams in critically ill septic patients comedicated with amikacin.

Objectives: The study aimed to characterize the pharmacokinetics (PK) of four β-lactams (piperacillin, ceftazidime, cefepime, and meropenem) in patients comedicated with amikacin (AMK), and to confirm the predictive performance of AMK data, obtained from therapeutic drug monitoring (TDM), on these PK, using a population modeling approach.

Design And Methods: Serum samples were collected in 88 critically ill septic patients. For each β-lactam, the covariate model was optimized using renal function.

A simultaneous d-optimal designed study for population pharmacokinetic analyses of mycophenolic Acid and tacrolimus early after renal transplantation.

Mycophenolic acid (MPA) and tacrolimus (TAC) are immunosuppressive agents used in combination with corticosteroids for the prevention of acute rejection after solid organ transplantation. Their pharmacokinetics (PK) show considerable unexplained intraindividual and interindividual variability, particularly in the early period after transplantation. The main objective of the present work was to design a study based on D-optimality to describe the PK of the 2 drugs with good precision and accuracy and to explain their variability by means of patients' demographics, biochemical test results, and physiological characteristics.

Acenocoumarol sensitivity and pharmacokinetic characterization of CYP2C9 *5/*8,*8/*11,*9/*11 and VKORC1*2 in black African healthy Beninese subjects.

This study aimed at investigating the contribution of CYP2C9 and VKORC1 genetic polymorphisms to inter-individual variability of acenocoumarol pharmacokinetics and pharmacodynamics in Black Africans from Benin. Fifty-one healthy volunteers were genotyped for VKORC1 1173C>T polymorphism. All of the subjects had previously been genotyped for CYP2C9*5, CYP2C9*6, CYP2C9*8, CYP2C9*9 and CYP2C9*11 alleles.

Population pharmacokinetic modeling and optimal sampling strategy for Bayesian estimation of amikacin exposure in critically ill septic patients.

Because the sepsis-induced pharmacokinetic (PK) modifications need to be considered in aminoglycoside dosing, the present study aimed to develop a population PK model for amikacin (AMK) in severe sepsis and to subsequently propose an optimal sampling strategy suitable for Bayesian estimation of the drug PK parameters. Concentration-time profiles for AMK were obtained from 88 critically ill septic patients during the first 24 hours of antibiotic treatment. The population PK model was developed using a nonlinear mixed effects modeling approach.

Comparative oral bioavailability of non-fixed and fixed combinations of artesunate and amodiaquine in healthy Indian male volunteers.

Objective: The aim of the present study was to compare the pharmacokinetic properties, bioavailability and tolerability of artesunate (AS) and amodiaquine (AQ) administered as a fixed-dose combination (Amonate FDC tablets; Dafra Pharma, Turnhout, Belgium) or as a non-fixed dose combination of separate AS tablets (Arsuamoon; Guilin Pharmaceutical Co, Shanghai, China) and AQ tablets (Flavoquine; Sanofi-Aventis, Paris, France).

Methods: This was a randomized, open label, two-period, two-treatment, two-sequence, cross-over study in which 60 healthy male Indian volunteers were given a single total oral dose of 100 mg AS and 400 mg AQ hydrochloride either as two tablets of Amonate FDC (AS 50 mg and AQ hydrochloride 200 mg) or as two AS tablets of the co-blister Arsuamoon (50 mg AS) together with two Flavoquine tablets (200 mg AQ hydrochloride). Plasma AS and blood AQ concentrations, as well as those of their respective active metabolites dihydroartemisinin (DHA) and desethylamodiaquine (DEAQ), were measured by high-performance liquid chromatography-tandem spectrometry.

Empirical models for dosage optimization of four beta-lactams in critically ill septic patients based on therapeutic drug monitoring of amikacin.

Objectives: The study aims to develop empirical models able to predict the pharmacokinetics (PK) of four beta-lactams using the amikacin (AMK) therapeutic drug monitoring (TDM), in order to optimize their dosage regimens.

Design And Methods: 69 critically ill septic patients were included. All received a first dose of AMK combined with piperacillin/tazobactam, ceftazidime, cefepime or meropenem.