Search

Published data suggest that therapeutic drug monitoring of human immunodeficiency virus protease inhibitors would improve the management of antiretroviral therapy. The authors have developed a high-pressure liquid chromatographic assay allowing simultaneous determination of six protease inhibitors (ritonavir, saquinavir, indinavir, nelfinavir, amprenavir, and lopinavir), using carbamazepine as internal standard. Detection was based on a dual wavelength ultraviolet spectrophotometer and can be improved by the use of a photodiode array detector. Monitoring was performed 1 month after initiation of therapy or in instances of therapeutic failure, side effects, suspicion of noncompliance, drug interactions, or malabsorption. Trough concentrations were 0.15 to 13.6 mg/L for ritonavir, 0.06 to 9.7 mg/L for indinavir, 0.03 to 5.5 mg/L for saquinavir, and 0.15 to 4.15 mg/L for nelfinavir. Concentrations below the limit of quantification were observed in 63/438 (14%) of the patients. Target concentrations are not well established, and reported in vitro inhibitory concentrations may be of limited value. The authors therefore chose to compare observed concentrations with mean plasma concentrations reported in clinical trials. Observed saquinavir and indinavir concentrations were often below or close to these target concentrations, particularly when used as a single protease inhibitor. Concentration-controlled studies should now be used to select proper target concentrations for each protease inhibitor, either prescribed alone or in combination.

The authors study the reactivation of B hepatitis virus in three HIV infected patients, correlating the moment of reactivation of and the CD4 and CD8 lymphocytes. Prior to the B viral reactivation, the three patients were with Ac HBc IgG (+) in serum, assessing that the presence of AC HBc IgG is insufficient to prevent the reactivation and to consider a B hepatitis cured. In two patients, prior to the B virus reactivation, AgHBs was (-) in the serum. It is considered that the predominant hepatocytolysis mechanism is the viral one, in the stage of B virus reactivation in patients with AIDS, the cell immunity mechanism being depressed.

The authors present 4 cases of chronic AgHBs positive hepatitis, with reactivations of hepatitis B virus. The reactivations occurred spontaneously, as mentioned in references. The authors appreciate that the cause of B virus reactivation bases upon factors which modify the immune status of the host. Alcohol is one of these factors, not yet mentioned in references as cause of virus B reactivation. Are also presented data about the existence of virus B mutants, in the studied patients, which could play a role in the reactivation of chronic hepatitis B.

Objectives: The aim of the present study was to compare the efficiency of pulmonary deposition of pentamidine using the Respirgard II jet nebuliser or the Fison ultrasonic nebuliser with 99m technetium (99m Tc) labelled pentamidine in the current conditions of recommended treatment. The study was designed in three stages, to verify particle size distribution, to validate the isotope labelling, and to compare pulmonary deposition of pentamidine isethionate with the two nebulisers., Methods: Count median aerodynamic diameter and mass median aerodynamic diameter were measured using the velocimetry technique and aerosol dispersion was calculated according to the standard deviation defined by the ratio of diameters between 84.3% and 50% of the total distribution. Stability of labelling was checked both in vitro, by radiochromatography, and in vivo, by the absence of free technetium thyroid fixation after intravenous injection of the preparation to a rat and inhalation by baboons. The direct isotopic technique was used to compare pulmonary deposition of 300 mg aerosolized 99m Tc labelled pentamidine isothionate with the two nebulisers in four HIV patients treated with primary prophylaxis., Results: Count median aerodynamic diameter and mass median aerodynamic diameter (MMAD) were higher with Fisoneb than with Respirgard II. Nevertheless Fisoneb MMAD remained in the optimal range for peripheral deposition. In one patient, pentamidine lung burden was higher using the Respirgard II (13% of dose originally in nebuliser) when compared with the Fisoneb (10.2% of dose originally in nebuliser). A better result was obtained in the 3 other patients with Fisoneb (mean = 14.3%) compared with Respirgard II (mean = 3.8%). In all 4 patients gastric contamination was higher with Fisoneb (mean = 5.2%) as compared with Respirgard II (mean = 2.6%). Cough and bronchospasm were not observed with either device., Conclusion: This study showed that Fisoneb, a practical and cheap nebuliser which has proved to be effective in clinical studies when used for pentamidine nebulisation, leads to correct particle size distribution and pulmonary deposition of the drug. We believe that such studies to evaluate aerosol characteristics should be recommended for any kind of nebuliser.

Isotopic techniques enable to determine the best conditions to aerosolize pentamidine as a preventive treatment of pneumocystis. An original labelling technique of pentamidine isethionate has led into a feasibility study of pentamidine scintigraphy in the monkey, and then to a clinical study. A tracer dose of 2 mg of pentamidine isethionate was diluted into 200 mg of pentamidine mesylate. An ultrasonic nebulizer (TV 6000) and a jet nebulizer (Venticis II) were first compared in four baboons. With the two nebulisers the curves of pulmonary kinetic activity showed a peak 10-15 minutes after the beginning of inhalation and then a plateau. With the ultrasonic TV6000 the pulmonary dose was on average 0.8 mg or 0.4% of the pentamidine aerosolized and the gastric contamination 3.1%. With the Venticis II compressed air apparatus the amount of pentamidine delivered to the deep lung was a mean of 4.2 mg or 2.1% of the aerosolized dose whereas the gastric contamination was only 0.5%. The delivery of the aerosol by the ultrasonic inhaler TV 6000 was then compared with two compressed air inhalers Venticis II and Respirgard II in four patients infected with HIV virus who were submitted to a preventative therapy against pneumocystis. With the ultrasonic TV 6000 the pulmonary dose was 0.8 mg or 0.3%-0.5% of the dose of pentamidine aerosolized and the digestive contamination was 3.1%. The performance of the two compressed air nebulizers Venticis II and Respirgard II were similar. The amount of pentamidine delivered to the deep lung was respectively 12 and 14 mg or 6 and 8% of the dose of pentamidine aerosolized and the digestive activity was 0.2%.(ABSTRACT TRUNCATED AT 250 WORDS)