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Biomedical subjects

D M Burger

Publications and source records attributed to D M Burger.

At least 55 records · Page 3Linked to original sources
PubMed1999

Simultaneous determination of the HIV-protease inhibitors indinavir, nelfinavir, saquinavir and ritonavir in human plasma by reversed-phase high-performance liquid chromatography.

A sensitive high-performance liquid chromatographic method has been developed for the simultaneous determination of the four licensed HIV-protease inhibitors indinavir, nelfinavir, saquinavir and ritonavir. An aliquot of 500 microl plasma, spiked with internal standard, was extracted with 0.5 ml 0.1 M NH4OH and 5 ml methyl tert.-butyl ether. After evaporating, the residue was dissolved in eluent consisting of acetonitrile-50 mM phosphate buffer, pH 5.63 (40:60, v/v). Subsequently, the eluent was washed with hexane. Chromatography was performed using a C18 reversed-phase column and gradient elution with a linear increase of acetonitrile from 36 to 66%. Ultraviolet detection at 215 nm was used. Linearity of the method was obtained in the concentration range of 45-30 000 ng/ml for all four analytes. The method was validated extensively and stability tests under various conditions were performed. The assay is now in use to analyse plasma samples from patients treated with (combinations of) HIV-protease inhibitors.

Anti-HIV Agents↗
PubMed1999

Urological complaints in relation to indinavir plasma concentrations in HIV-infected patients.

OBJECTIVE: To assess the relationship between indinavir-associated urological complaints and indinavir plasma concentrations. DESIGN: Case series, comparing indinavir plasma concentrations in cases with average concentrations in a control group. METHODS: Patients taking 800 mg indinavir three times a day (tid), who presented with overt urological complaints (renal colic, flank pain or haematuria) were selected for the study. Plasma indinavir concentrations were measured by means of a standardized high performance liquid chromatography (HPLC) method. Plasma samples taken at 1.5-8 h after the last indinavir ingestion were included for evaluation. Results were compared with the full pharmacokinetic curves of indinavir plasma concentrations from a control group of 14 patients taking 800 mg indinavir tid without urological complaints, and were expressed as concentration ratios. A ratio of 1 indicated a plasma concentration equalling the average concentration in the control population at the same point in time after the ingestion of indinavir. RESULTS: Seventeen patients (five women) were enrolled and the indinavir concentrations of 15 patients could be evaluated. Fourteen (93%) patients had a concentration above the mean of the controls, 12 (80%) patients had a concentration above the upper 95% confidence limit, and one (7%) patient had a concentration below the lower 95% confidence limit. The mean indinavir concentration in patients with urological complaints (ratio range 0.55-11.49) was significantly higher than the average concentration and the upper 95% confidence limit of the control group (P < 0.05). The results could not be explained by differences in weight, sex or drug interactions. Two patients had chronic active hepatitis B infection. In six patients with indinavir concentrations above the upper 95% limit, indinavir was reduced to 600 mg tid. Upon repeat measurement after the dose adjustment, their indinavir plasma concentrations fell within the 95% confidence interval around the mean of the control population. All six patients remained asymptomatic and had viral loads of less than 500 copies per ml after a follow-up of 5-16 months. CONCLUSIONS: Urological complications occurring during indinavir treatment were associated with elevated indinavir plasma concentrations in 80% of patients in this study. Indinavir plasma concentrations should be monitored upon presentation of urological complaints, on the basis of which dose reductions may be applied if brief interruption and increased hydration are ineffective.

Adult↗
PubMed1999

Long-term stability of morphine and bupivacaine mixture for spinal use.

From clinical studies it has been proven that morphine in combination with bupivacaine is applicable in cancer pain. The availability of a ready to use parental dosage form of morphine and bupivacaine is comfortable for health care workers. Stability of a morphine or a bupivacaine preparation or a combination of both in a PVC cassette or polypropylene syringe for spinal use is examined in several studies. Apart from one study no data on long-term stability of morphine-bupivacaine mixture is available. A forced degradation study and a shelf-life study at room temperature (20-25 degrees C) were started on morphine hydrochloride 0.2 mg/ml and bupivacaine hydrochloride 7.5 mg/ml in 50 ml sterilized glass bottles type II. The results of the stability study showed that this mixture was stable up to 18 months at room temperature, whereafter morphine showed a slight degradation (5%) and bupivacaine remained stable.

Analgesics, Opioid↗
PubMed1999

Stability of dithranol in creams.

The stability of the anthrachinone derivative dithranol in creams was studied during storage at temperatures of 4 degrees C and 20 degrees C. Aluminum-coated tubes with 0.1, 0.3 and 0.5% dithranol were stored and samples were analysed immediately and after 3, 6 and 12 months of storage. The 0.3% dithranol cream was also stored in polypropylene tubes. Drug concentration was analysed by high-performance liquid chromatography. All concentrations tested were stable for 12 months of storage at 4 degrees C in aluminum-coated tubes. This means that these low concentrations are sufficiently stable to be prepared in advance for at least 12 months if prepared as described and kept refrigerated. Polypropylene tubes should not be used.

Administration, Topical↗
PubMed1998

Managing drug reactions to sulfonamides and other drugs in HIV infection: desensitization rather than rechallenge?

Drug reactions in patients with HIV infection, e.g. fever or rash, are a frequently occurring clinical problem. These side effects particularly are observed with sulfonamides; however, many other drugs have also shown to induce allergic reactions when given to patients with HIV infection. The production of hydroxylamines has been put forward as one of the explanations for these high incidence of reactions on drugs. Since sulfonamides are the first choice of therapy for the treatment and prophylaxis of Pneumocystis carinii pneumonia, several strategies have been developed to circumvent drug reactions. In general rechallenge or desensitization are recommended in literature. This article discusses the results and risks of rechallenge and desensitization with sulfonamides or other drugs, as mentioned in the literature. Furthermore preliminary results of rechallenge with a sulfonamide, which is not metabolized into hydroxylamines, are presented. From the data in the literature it is concluded that desensitization should be preferred to rechallenge.

Anti-Infective Agents↗
PubMed1998

Low plasma concentrations of indinavir are related to virological treatment failure in HIV-1-infected patients on indinavir-containing triple therapy.

All human immunodeficiency virus type 1 (HIV-1)-infected patients who started to use indinavir (800 mg three times a day) as part of their triple drug regimen were included in a study to determine the importance of low plasma concentrations of indinavir as a cause of virological treatment failure. The indinavir concentration and a number of patient characteristics at baseline were tested as risk factors for virological treatment failure (defined as a viral load above 200 copies/ml after 24 weeks of treatment) in univariate and multivariate analyses; 65 patients were included. Virological treatment failure occurred in 36.9% of the patients. Multivariate analysis showed that a low plasma concentration of indinavir (odds ratio 0.1), a high viral load at baseline (odds ratio 2.6) and pretreatment with another protease inhibitor (odds ratio 10.0) were independent factors related to virological treatment failure. Monitoring of indinavir plasma concentrations may be an important tool for the optimization of triple drug combination therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Determination of indinavir, an HIV-protease inhibitor, in human plasma by reversed-phase high-performance liquid chromatography.

A sensitive high-perforrmance liquid chromatographic assay has been developed to determine the concentrations of the HIV-protease inhibitor indinavir in human plasma. The sample pretreatment involved a protein precipitation procedure using 100 microl of human plasma and 400 microl of acetonitrile. Chromatography was carried out on an Octadecyl column using a mobile phase of acetonitrile-water (40:60, v/v). The water phase contained 50 mM phosphate buffer pH 6 and 4 g/l tetramethylammoniumchloride. Ultraviolet detection at 210 nm was used. The method has been validated with regard to specificity, detection limit, lower and upper limit of quantitation, recovery, accuracy, and inter- and intra-assay precision. Stability tests under various conditions were performed. The bioanalytical assay is now in use for the determination of indinavir in several clinical pharmacokinetic studies in HIV-infected patients.

Acetonitriles↗
PubMed1997

Penetration of 3'-amino-3'-deoxythymidine, a cytotoxic metabolite of zidovudine, into the cerebrospinal fluid of HIV-1-infected patients.

The penetration of 3'-amino-3'-deoxythymidine (AMT) into the cerebrospinal fluid (CSF) of HIV-1-infected patients has been investigated. In 23 patients who used zidovudine (ZDV) chronically, CSF and plasma samples were assayed for AMT and ZDV. The influences of time between ZDV oral administration and lumbar puncture, of ZDV dose, and of the medical indication for lumbar puncture based on the concentration of AMT in CSF and on the CSF-plasma concentration ratio were investigated. AMT can be detected in the CSF after oral administration of ZDV; concentrations of AMT in CSF ranged from 0.75 to 4.8 ng/ml (median, 1.7 ng/ml). The median CSF-plasma concentration ratio was 1, and equaled that for ZDV. CSF and plasma concentrations of AMT were approximately threefold higher in patients with cerebral toxoplasmosis; the CSF-plasma concentration ratio remained equal to unity in these cases. This phenomenon might be caused by a pharmacokinetic interaction between AMT and pyrimethamine, sulfadiazine, folinic acid, or a combination of these. The clinical relevance of AMT, especially the possibility of decreased efficacy of ZDV, throughout the body and in the central nervous system, and the involvement of this metabolite in ZDV-induced myelosuppression, remains to be established.

Administration, Oral↗
PubMed1997

Clinical pharmacology of HIV protease inhibitors: focus on saquinavir, indinavir, and ritonavir.

In this review the clinical pharmacology of HIV protease inhibitors, a new class of antiretroviral drugs, is discussed. After considering HIV protease function and structure, the development of inhibitors of HIV protease is presented. Three protease inhibitors are reviewed in more detail: saquinavir, indinavir, and ritonavir. Clinical trial results with these agents are evaluated. Furthermore, adverse effects, resistance, dosage and administration, clinical pharmacokinetics, pharmacokinetic-pharmacodynamic relationships, and drug interactions are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Clinically relevant drug interactions with antiretroviral agents.

With the advent of the human immunodeficiency virus (HIV) protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, the importance of drug-drug interactions with antiretroviral agents is becoming increasingly recognized. Every clinician involved in the care of HIV-infected persons should have a broad knowledge of these drug-drug interactions and their underlying mechanisms. This paper will review currently known clinically relevant interactions with antiretroviral agents reported thus far. Alternative strategies will be proposed where possible, in order to improve patient safety and the therapeutic efficacy of the antiretroviral agents. It must be emphasized, however, that in many cases these proposals are not backed up by authoritative clinical consensus panels and that clinical experience with many of these combinations is limited.

Anti-HIV Agents↗
PubMed1997

HIV-1 RNA levels in the cerebrospinal fluid may increase owing to damage to the blood-brain barrier.

Human immunodeficiency virus type 1 (HIV-1) RNA can be detected in the cerebrospinal fluid (CSF) of 75-90% of all HIV-infected patients. However, it is not yet known which factors influence the amount of HIV-1 in the CSF, either qualitatively or quantitatively. We have analysed HIV-1 RNA in CSF samples from 24 HIV-infected patients using zidovudine who underwent lumbar puncture in order to establish a diagnosis for a neurological disorder. Several factors were examined for possible correlation with the amount of HIV-1 RNA in the CSF: age, gender, the medical indication for lumbar puncture, the most recent CD4 cell count in blood, zidovudine dose, duration of treatment with zidovudine, the zidovudine concentration in plasma and CSF, and the total protein concentration in plasma and CSF. The only statistically significant factor was the total protein level in the CSF, which showed a positive relation with the amount of HIV-1 RNA in the CSF. This study indicates that increased levels of HIV-1 RNA in the CSF of neurologically symptomatic patients are the result of damage to the blood-brain barrier.

AIDS Dementia Complex↗
PubMed1996

[Acanthamoeba keratitis].

Three patients, women aged 69, 25 and 30 years, with refractory keratitis were found to have a rare infection with Acanthamoeba. All wore soft contact lenses. The frequency of Acanthamoeba keratitis increased in recent years. At present, an efficacious antiprotozoal therapy is available, for instance in the form of polyhexamethylene biguanide and propamidine. In cases of refractory keratitis, the possibility of an Acanthamoeba infection should be taken into account.

Acanthamoeba Keratitis↗