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Biomedical subjects

C Lamotte

Publications and source records attributed to C Lamotte.

6 recordsLinked to original sources
PubMed1999

Determination of nelfinavir, a potent HIV protease inhibitor, and its active metabolite M8 in human plasma by high-performance liquid chromatography with photodiode-array detection.

We developed and characterized a high-performance liquid chromatographic assay for the determination of nelfinavir (NFV), a potent HIV protease inhibitor, and its active metabolite M8 in human plasma. Extraction of the internal standard, M8 and NFV from the plasma buffered at pH 9.5 was achieved by a liquid-liquid extraction with a mixture of methyl-tert.-butyl ether and hexane. Following two washes of the reconstituted sample with hexane, separation was achieved on an octadecylsilyl analytical column with a mobile phase containing 0.1% trifluoroacetic acid-acetonitrile-methanol (51:46:5, v/v). Detection was performed using an ultraviolet photodiode-array detector. The signal was monitored at a wavelength of 220 nm. The assay was found to be linear and has been validated over the concentration range of 25 to 3000 microg/l for M8 and 25 to 6000 microg/l for NFV, from 500 microl of plasma. Recoveries were 98.9% (SD 8.9%), and 100.2% (SD 11.7%) for M8 and NFV, respectively. Concentrations that gave a signal-to-noise ratio of three (15 microg/l for both M8 and NFV) were selected to determine the limit of detection. The lower limit of quantification (25 microg/l for both M8 and NFV) was defined as the concentration for which the relative standard deviation and the percent deviation from the nominal concentration were lower than 20%.

Anti-HIV Agents↗
PubMed1999

Kinetics of antiviral activity and intracellular pharmacokinetics of human immunodeficiency virus type 1 protease inhibitors in tissue culture.

We have examined the kinetics of the inhibition of human immunodeficiency virus type 1 (HIV-1) particle infectivity by protease inhibitors (PIs) in cell culture, using either transfected HeLa cells or infected peripheral blood mononuclear cells (PBMCs) as producers of infectious virions. Both the kinetics of the initiation of antiviral activity after addition of the PIs to these cultures and the kinetics of restoration of virion infectivity after removal of the PIs from the treated cultures were examined. We found that the kinetics of initiation of particle infectivity inhibition produced by a high extracellular concentration (5 microM) of the inhibitors were similar for all five inhibitors tested: loss of particle infectivity was perceptible as early as 1 h after the initiation of PI treatment and increased gradually thereafter. By contrast, the durability of this antiviral effect following removal of the drug from the culture varied dramatically according to the drug studied. In transfected HeLa cells, saquinavir and nelfinavir exerted the most prolonged inhibition, with the half-lives of their antiviral activities being greater than 24 h, while ritonavir exerted an intermediate length of inhibition (18 h) and indinavir and amprenavir exerted a reproducibly shorter length of inhibition (5 h). For all five tested PIs, these kinetics were significantly faster in PBMCs than in HeLa cells. The striking differences in antiviral kinetics observed among the different PIs appear mostly due to differences in their intracellular concentrations and/or rates of cellular clearance. Our observations, although limited to tissue culture conditions, may help delineate the cellular parameters of the antiviral activities of HIV-1 PIs and further optimize the efficiencies of these antiretrovirals in vivo.

Antiviral Agents↗
PubMed1989

[Does nimodipine improve the outcome of perioperative complications of aneurysm rupture? Results of systematic treatment].

Morbidity after aneurysmal subarachnoid hemorrhages is proceeding from many factors; ischemic etiology is underestimated and frequently thought to be vasospasm related only. Other undoubted mechanisms are in the setting of ischemic disorders after ruptured aneurysms. The management of these disorders is relevant of new calcium blockers. Early administration of prophylactically oral nimodipine, with temporary intravenous administration of the therapy after surgery or in the setting of delayed ischemic deterioration, were assigned to 36 patients with aneurysm surgery. Efficacy was judged on prevention and outcome of ischemic disorders at discharge and three months later using the Glasgow Outcome Scale. On all, twenty-nine patients were disabled from any etiology; twenty made full or improved recoveries at discharge; twenty-eight get independent conditions of life at 3 months. Fourteen patients have return to their pre-rupture activity. Twenty-two surgical patients (61%) set an undoubtly ischemic disability during any time of their hospitalization, but many etiologies were identified in majority of cases. Spasm is the main factor of stroke in only 6 patients, and one of the ischemic factors in 15 cases. Among these ischemic deteriorations, twenty improved or made full recovery at discharge and get independent life at 3 months. No death with spasm. These data support the assumption that vasodilatating is not the only mode of nimodipine action. Hypervolemia must be adjunct with nimodipine to prevent regional hypoperfusion.

Adolescent↗