Single-step extraction of fluconazole from plasma by ultra-filtration for the measurement of its free concentration by high performance liquid chromatography.

High performance liquid chromatography (HPLC) is the reference method for measuring concentrations of antimicrobials in blood. This technique requires careful sample preparation. Protocols using organic solvents and/or solid extraction phases are time consuming and entail several manipulations, which can lead to partial loss of the determined compound and increased analytical variability.

Transplacental passage of protease inhibitors at delivery.

Objective: Although combinations of different antiretroviral drugs are increasingly used by pregnant HIV-1-infected women, few human data are available to evaluate in utero protease inhibitors (PI) exposure. The aim of this study was to assess the extent of transplacental passage of PI at delivery.

Methods: Pregnant women treated with antiretroviral drugs including PI and/or nevirapine were eligible for the study.

Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients.

Objectives: To determine fluconazole population pharmacokinetics and explore the relationships between fluconazole average concentration and treatment effectiveness or microbiological resistance induction during a study aimed at evaluating the efficacy, tolerability and resistance induction after secondary prevention with fluconazole (150 mg weekly) versus placebo in human immunodeficiency virus-positive (HIV+) patients with oropharyngeal candidiasis.

Methods: Population pharmacokinetic parameters of fluconazole determined from 458 serum drug concentration measurements obtained over 37 months in 132 HIV + patients not receiving highly active antiretroviral therapy. Mean estimates and variabilities were generated using non-linear regression analysis.

Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study.

Background: HIV-1-infected patients vary considerably by their response to antiretroviral treatment, drug concentrations in plasma, toxic events, and rate of immune recovery. This variability could have a genetic basis. We did a pharmacogenetics study to analyse the association between response to antiretroviral treatment and allelic variants of several genes.

Nelfinavir plasma levels under twice-daily and three-times-daily regimens: high interpatient and low intrapatient variability.

Nelfinavir has been recently approved as a twice-daily (BID) dose regimen, but no evaluation of the influence of this regimen change on patients' protease inhibitor exposure has been published. The aim of this study was to compare trough plasma concentrations of nelfinavir obtained under the 1250-mg b.i.

Diet acids and alkalis influence calcium retention in bone.

The urine-acidifying properties of food constituents depend on their content of non-oxidizable acids or precursors. Acidifying constituents such as animal proteins may negatively affect calcium metabolism and accelerate bone resorption, thus representing an aggravating factor for osteoporosis. This four-period, double-crossover study investigated whether a diet intervention specifically focused on acid load could modify calcium metabolism in humans.

Midazolam premedication reduces propofol dose requirements for multiple anesthetic endpoints.

Purpose: This study investigates the interactions between midazolam premedication and propofol infusion induction of anesthesia for multiple anesthetic endpoints including: loss of verbal contact (LVC; hypnotic), dropping an infusion flex (DF; motor), loss of reaction to painful stimulation (LRP; antinociceptive) and attainment of electroencephalographic burst suppression (BUR; EEG).

Methods: In a double blind, controlled, randomized and prospective study, 24 ASA I-II patients received either midazolam 0.05 mg x kg(-1) (PM; n = 13) or saline placebo (PO; n = 11) i.

Extractionless method for the simultaneous high-performance liquid chromatographic determination of urinary caffeine metabolites for N-acetyltransferase 2, cytochrome P450 1A2 and xanthine oxidase activity assessment.

Urinary metabolic ratios of caffeine are used in humans to assess the enzymatic activities of cytochrome P450 isoenzyme 1A2 (CYP1A2), xanthine oxidase (XO) and for phenotyping individuals for the bimodal N-acetyltransferase 2 (NAT2), all of them involved in the activation or detoxification of various xenobiotic compounds. Most reported analytical procedures for the measurement of the urinary metabolites of caffeine include a liquid-liquid extraction of urine samples prior to their analysis by reversed-phase HPLC. At neutral to basic pH however, 5-acetylamino-6-formylamino-3-methyluracil (AFMU), a metabolite of caffeine, spontaneously decomposes to 5-acetylamino-6-amino-3-methyluracil (AAMU).

Validation of an AAS method for the determination of platinum in biological fluids from patients receiving the oral platinum derivative JM216.

A flameless atomic absorption spectrometric (AAS) method has been developed and validated for the determination of platinum (Pt) in human plasma, plasma ultrafitrate and urines from cancer patients receiving the orally available platinum derivative, JM216. Sample pretreatment is minimal for urine, which is diluted with 10% HCl prior to AAS analysis. Pt analysis in plasma requires the application of the matrix modifier 5% Triton X-100 directly onto the integrated L'vov platform of the graphite furnace prior to the addition of plasma samples.

Validation of an HPLC method for the determination of urinary and plasma levels of N1-methylnicotinamide, an endogenous marker of renal cationic transport and plasma flow.

N1-Methylnicotinamide (NMN) is an endogenous cationic metabolite of nicotinamide (niacine, vitamine PP) whose renal clearance reflects both the capacity of the renal tubular transport system to secrete organic cations and renal plasma flow. NMN is present in human plasma and urine at the 1-117-ng ml(-1) and 0.5-25-microg ml(-1) concentration range, respectively, and its level depends notably on pathophysiological (age, renal or hepatic diseases) conditions.

Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients.

Objective: Limited information exists on the clinical usefulness of drug level monitoring for efavirenz, a once-daily non-nucleoside reverse transcriptase inhibitor (NNRTI). The aim of this study was to determine whether efavirenz plasma concentration monitoring could predict treatment failure and central nervous system (CNS) tolerability.

Methods: Blood samples were obtained from 130 HIV-infected patients receiving efavirenz in combination with other antiretroviral agents for more than 3 months.

Continuous infusion of ceftazidime with a portable pump is as effective as thrice-a-day bolus in cystic fibrosis children.

Unlabelled: Continuous infusion (CI) of beta-lactam antibiotics provides a stable concentration which may result in a better activity against gram-negative bacteria if exceeding the minimum inhibitory concentration (MIC). Treatment outcome after 24 h CI of ceftazidime (CAZ) in cystic fibrosis (CF) children was compared with the bolus administration regimen. Fourteen CF children with chronic Pseudomonas aeruginosa pulmonary infection were treated during 14 days with the conventional CAZ thrice-a-day bolus infusion (regimen A), and few months later with 24 h Cl of CAZ (regimen B) using a portable pump.

Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir, nelfinavir and the non-nucleoside reverse transcriptase inhibitor efavirenz by high-performance liquid chromatography after solid-phase extraction.

As part of an on-going study on the suitability of a formal therapeutic drug monitoring (TDM) of antiviral drugs for improving the management of HIV infection, a high-performance liquid chromatography method has been developed to quantify simultaneously in plasma five HIV protease inhibitors (PIs) (i.e., indinavir, amprenavir, saquinavir, ritonavir, nelfinavir) and the novel non-nucleoside reverse transcriptase inhibitor efavirenz.

Midazolam premedication and thiopental induction of anaesthesia: interactions at multiple end-points.

We have studied the effects of midazolam premedication on multiple anaesthetic end-points (hypnotic, loss of verbal contact (LVC); motor, dropping an infusion flex or bag (DF); analgesic, loss of reaction to painful stimulation (LRP); and EEG, attainment of burst suppression (BUR)) during induction by slow thiopental infusion at a rate of 55 mg kg-1 h-1. Patients received midazolam 0.05 mg kg-1 i.

The ribonucleoside diphosphate reductase inhibitor (E)-2'-deoxy-(fluoromethylene)cytidine as a cytotoxic radiosensitizer in vitro.

(E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC) is known as an inhibitor of ribonucleoside diphosphate reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.

Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours.

Background: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine.

Trace lithium in mood disorders.

Background: Variations in trace (endogenous) lithium exchanges have been postulated to play a role in the pathophysiology of affective diseases. This prospective study aimed to check whether plasma, erythrocytes and urine trace lithium levels were altered in mood disorders.

Methods: Trace lithium was determined by atomic absorption spectrophotometry in patients without mood stabilizing drugs or somatic diseases, hospitalized for bipolar affective disorders, major depressive episodes, and other psychiatric disorders with depressive features.

Simultaneous determination of deoxyribonucleoside in the presence of ribonucleoside triphosphates in human carcinoma cells by high-performance liquid chromatography.

Simultaneous determination of ribonucleoside and deoxyribonucleoside triphosphates in cells by HPLC is an analytical challenge since the concentration of dNTP present in mammalian cells is several orders of magnitude lower than the corresponding NTP. Hence, the quantitation of dNTP in cells is generally performed after selective oxidation or removal of the major NTP. The procedures reported so far are lengthy and cumbersome and do not enable the simultaneous determination of NTP.

Effects of a dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, MDL 100,240, on endocrine and renal functions in healthy volunteers.

Objective: To investigate the endocrine and renal effects of the dual inhibitor of angiotensin converting enzyme and neutral endopeptidase, MDL 100,240.

Design: A randomized, placebo-controlled, crossover study was performed in 12 healthy volunteers.

Methods: MDL 100,240 was administered intravenously over 20 min at single doses of 6.

Pharmacokinetics of temozolomide in association with fotemustine in malignant melanoma and malignant glioma patients: comparison of oral, intravenous, and hepatic intra-arterial administration.

Purpose: Depletion of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AT) has been shown to increase tumor sensitivity to chloroethylnitrosoureas. Temozolomide (TMZ), an analogue of dacarbazine, can deplete AT, suggesting that it may be used to sensitize tumors to chloroethylnitrosoureas. However, the influence of nitrosoureas on the pharmacokinetics of TMZ is unknown, and a pilot study was performed to assess the pharmacokinetics of TMZ given via, various routes to 29 patients (27 malignant melanomas, 2 gliomas) with or without sequential administration of i.

Determination of trace lithium in human erythrocytes by electrothermal atomic-absorption spectrometry with pyrocoated graphite tubes and integrated platform.

Electrothermal graphite-furnace atomic-absorption spectroscopy with pyrocoated graphite tubes, integrated platform and matrix modification was used to determine submicromolar concentrations of trace lithium in human red blood cells. Matrix-matched samples were used to establish calibration curves for concentrations up to 0.58 microM (addition-calibration method) with satisfactory linearity (r2 > 0.

Specific determination of PAH and its N-acetyl metabolite by HPLC increases the accuracy and precision of PAH clearance measurements.

PAH (N-(4-aminobenzoyl)-glycin) clearance measurements have been used for 50 years in clinical research for the determination of renal plasma flow. The quantitation of PAH in plasma or urine is generally performed by colorimetric method after diazotation reaction. Although straightforward, the measurements must be corrected for the nonspecific residual response observed in blank plasma.

Estimation of glomerular filtration rate by sinistrin clearance using various approaches.

Two protocols for the determination of glomerular filtration rate (GFR) from sinistrin clearance are considered: a bolus injection and a bolus followed by infusion. On both occasions, serial blood and urine samplings are scheduled up to 6 h. Four calculation methods are compared for estimating GFR from the data obtained during each protocol: classical UV/P (ratio of urinary excretion rate over plasma concentration) after bolus or bolus plus infusion; 2-point (log-linear slope multiplied by apparent volume of distribution); D/AUC (ratio of dose over area under the curve) after bolus; and Rin/P (ratio of infusion rate over steady-state concentration) during infusion.

Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients.

Objective: To compare the acute and sustained renal hemodynamic effects on hypertensive patients of 100 mg irbesartan and 20 mg enalapril each once daily.

Patients: Twenty patients (aged 35-70 years) with uncomplicated, mild-to-moderate essential hypertension and normal serum creatinine levels completed this study.

Study Design: After random allocation to treatment (n=10 per group), administration schedule (morning or evening) was determined by further random allocation, with crossover of schedules after 6 weeks' therapy.