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Biomedical subjects

C Harvengt

Publications and source records attributed to C Harvengt.

At least 127 records · Page 7Linked to original sources
PubMed1982

Distribution of daunorubicin intravenously injected or intravenously infused as free drug and as a complex with DNA in rabbits.

The tissue distribution of daunorubicin (DNR) was investigated in rabbits after 5 mg/kg DNR i.v. bolus injection or 4 h infusion of 5 mg/kg either as free drug or as a complex with DNA. After i.v. bolus, the highest DNR concentration was observed in lungs and kidneys, a lower concentration in heart and spleen and the least in the liver. The DNR biotransformation to daunorubicinol (DNR-ol) and aglycones was most active in kidneys and liver, while heart, lungs and spleen metabolized DNR to a lower extent. The DNR tissue elimination half-life varied from 4.5 to 8.7 h, whereas concentrations of DNR-ol remained elevated for a longer period of time. After 4 h infusion, the only difference when compared with i.v. bolus consisted of a 3-fold lower initial DNR concentration in heart and lungs. No striking difference could be observed after free versus complexed drug infusion except for a somewhat lower DNR concentration in heart and lungs for the complexed drug.

Animals↗
PubMed1982

Effect of hemodialysis on plasma kinetics of fenofibrate in chronic renal failure.

The influence of hemodialysis on plasma fenofibric acid kinetics has been investigated in patients with chronic renal failure given 300 mg of fenofibrate in a single oral dose. A very pronounced lengthening of the fenofibric acid plasma decay was observed in both hemodialyzed (n = 6) and nonhemodialyzed (n = 9) patients. Hemodialysis did not modify the plasma levels and the ultrafiltrates contained very small amounts of fenofibric acid. The repeated daily administration of 100 mg of fenofibrate during 2 weeks in 5 renal patients on regular hemodialysis resulted in increasing plasma levels and led to progressive cumulation of fenofibric acid. Plasma fenofibric acid conjugates could not be detected. No particular clinical side effects or increase of CPK, GOT, GPT were be observed.

Adult↗
PubMed1982

The pharmacokinetics of dl- and l-moprolol in the human.

The pharmacokinetics of a single dose (75 mg) of dl-moprolol and l-moprolol, a new beta -blocking agent, were appraised over 3 days in two groups of ten volunteers. The peak plasma level (GLC method) (598 +/- 99 ng/ml), the area under the curve (3.054 +/- 578 ng.ml/h), and 24-h urinary excretion (34.83 +/- 6.33 mg) after 1-moprolol intake were more elevated than after dl-moprolol intake. However, the plasma elimination half-life was not statistically different, 2.3 +/- 0.26 h after 1-moprolol versus 2.11 +/- 0.3 h after dl-moprolol. The double product (systolic blood pressure x heart rate) was significantly decreased only in volunteers after receiving 1-moprolol but not after dl-moprolol. The mean pharmacodynamic half-life estimated from exercise heart rate after dl-moprolol was 11.6 h.

Adrenergic beta-Antagonists↗
PubMed1981

Plasma lipid concentrations and lecithin:cholesterol acyltransferase activity in normolipidemic subjects given fenofibrate and colestipol.

Plasma lipids and lipoprotein cholesterol concentrations and lecithin:cholesterol acyltransferase activity were measured in 7 normolipidemic subjects before, and 7 days after, the administration of fenofibrate (300 mg daily) and colestipol (15 g daily) taken separately or simultaneously. Fenofibrate provoked a significant decrease in the mean plasma triglycerides (26%) and cholesterol (10%) concentration; only plasma cholesterol concentrations were significantly lowered by colestipol (26%). The cholesterol lowering effects of the two drugs were additive as was observed when colestipol was added to fenofibrate. The mean plasma high density lipoprotein cholesterol (HDL-C) concentration was significantly increased by fenofibrate (10%) and when colestipol was added to fenofibrate (15%), but not by colestipol alone. Both fenofibrate and colestipol caused significant reduction of the mean plasma low density lipoprotein cholesterol (LDL-C) concentration and the mean plasma LDL-C/HDL-C ratio (13% and 18%, respectively, with fenofibrate, 44% and 52% with colestipol, and 53% and 62% with colestipol added to fenofibrate). The mean plasma fractional esterification rate was significantly increased by 25% and 12%, respectively, with fenofibrate and colestipol when taken separately, and still more (91%) when colestipol was added to fenofibrate. The mean plasma molar esterification rate was significantly lowered by colestipol, but remained unchanged with the other drug regimens. This study shows that fenofibrate and colestipol given to normolipidemic subjects can induce in a very short period of time (7 days) marked changes in lipoprotein metabolism. Interpretations of the findings in relation to lipoprotein metabolism are discussed.

Adult↗
PubMed1981

Cefotaxime kinetics after multiple-dose intramuscular study in healthy volunteers.

The pharmacokinetics of cefotaxime after repeated doses of intramuscular injections were studied in 8 healthy volunteers receiving 1 g cefotaxime every 8 h for 6 days. Mean peak serum level after the first 1 g intramuscular dose was 26.8 +/- 6.4 micrograms/ml and the peak serum concentration was reached within 75 min. The half-life of cefotaxime was 1.35 +/- 0.33 h and the total apparent clearance 263 +/- 63 ml/min. After the last injection (day 6), the mean peak serum level reached 19.1 +/- 3.2 micrograms/ml and the areas under the curve were significantly lower than on day 1. No body accumulation of the drug could be detected. Serum levels of cefotaxime monitored throughout the study 5 min prior to and 30 min after the intramuscular injection were found above the minimum inhibitory concentration for most aerobic gram-positive and gram-negative sensitive organisms.

Adult↗
PubMed1980

[Pharmacokinetics of fenofibrate in man (author's transl)].

The active metabolite of fenofibrate is fenofibric acid, which is strongly bound to serum proteins. Following a single oral dose of 300 mg fenofibrate there is a diphasic decrease in plasma levels of fenofibric acid, and most of the drug is excreted as conjugate in the urine. Following daily oral administration of 300 mg during 10 days, a state of equilibrium is obtained within 2 to 3 days and persists throughout the observation period; the mean elimination half-life and urinary excretion rate are very similar to those measured after a single dose, and the drug does not accumulate. In patients with renal insufficiency, the plasma half-life of fenofibric acid is very substantially prolonged and considerable accumulation takes place, as the compound is virtually not dialyzable. Doses of 100 mg/day produce plasma levels similar to those obtained with 300 mg/day. The lipid-lowering activity mostly affects triglycerides. Concomitant administration of colestipol has no effect on blood kinetics and urinary excretion of fenofibrate but results in very important reduction of all lipoprotein fractions.

Colestipol↗
PubMed1980

Uricosuric effect of fenofibrate in healthy volunteers.

The uricosuric properties of a single oral dose (300 mg) of fenofibrate, or isopropyl-[4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl] propionate (LF 178), a new hypolipidemic drug, have been investigated versus placebo, benzbromarone, with and without urine alkalinization, in ten normouricemic male volunteers, following a crossover design. Twofold increased uric acid clearance values were obtained after fenofibrate and fourfold increased values after benzbromarone. The ratio urinary uric acid/urinary creatinine (UUA/UCr) was enhanced after fenofibrate and benzbromarone versus placebo. The urine alkalinization with fenofibrate intake did increase this ratio to a higher extent.

Adult↗
PubMed1980

Lack of pharmacokinetic interaction of colestipol and fenofibrate in volunteers.

The possibility of a pharmacokinetic interaction between two hypolipidemic drugs, colestipol, an ion exchange resin, and fenofibrate, a phenoxyacid derivative, was studied in 6 male volunteers. The investigation followed a four-step protocol during 18 days, and relied on determination of plasma and urinary levels of fenofibric acid, the active metabolite of fenofibrate. The kinetics of a single dose of fenofibrate 300 mg was established over 3 days. Thereafter, from Days 4 to 9 fenofibrate was given daily as 200 mg in the morning and 100 mg in the evening; the plasma fenofibric acid level reached about 10 microgram/ml. From Days 9 to 15 the same dose of fenofibrate was administered together with colestipol 10 g in the morning and 5 g in the evening. Plasma fenofibric acid concentrations remained unchanged and the 24 h urinary excretion of fenofibric acid did not fall. On day 15, a last single dose of fenofibrate 300 mg was given with colestipol 15 g. The pharmacokinetic pattern of fenofibric acid on Days 15 to 18 did not differ significantly from that found previously (Days 1 to 3). From these results, it is likely that there is no pharmacokinetic interaction between the two hypolipidemic drugs.

Adult↗
PubMed1980

Hypolipidemic and hypouricemic action of fenofibrate in various types of hyperlipoproteinemias.

Fenofibrate, a phenoxyacid derivative, given at daily dose of 300mg during 1 year following a single blind design, lowered significantly serum triglycerides and total cholesterol in patients various types of hyperlipoproteinemias (IIa, IV, V), fibrate significantly reduced plasma uric acid. Side effects were few after prolonged treatment. Moderate and transient increases in creatine phosphokinase and glutamopyruvic transaminase values were shown in some patients. An interaction with oral anticoagulants was also observed.

Adult↗
PubMed1979

Human pharmacokinetics of the daunorubicin-DNA complex. An alternative view of the lysosomotropic theory.

Plasma kinetics and urinary execretion of daunorubicin (DNR) and its active metabolite, daunorubicinol (DNR-ol) were studied in 15 leukemic patients after a 4-h infusion of 75 mg DNR/m2 either as the free drug or as a complex with DNA. The data obtained after infusion of the DNR-DNA complex were compared with the data obtained after infusion of the free drug. The DNR plasma levels were found to be higher during the 2 h following the infusion of the complex; the levels of DNR-ol were only higher for a few minutes after infusion. Kinetic analysis showed that complexing with DNA does not fundamentally modify the three-compartment model described for DNR. Only quantitative modifications were observed: a marked lengthening of the alpha-phase and a shortening of the gamma-phase. Urinary excretion of DNR and DNR-ol was increased after infusion of the complexed drug, in relation to the persistence of higher plasma levels. The data recorded in this work do not confirm the lysosomotropic mechanism postulated for the DNR-DNA complex, but show a delayed distribution of DNR, which is progressively released by dissociation of the circulating DNR-DNA complex, as previously demonstrated in rabbits infused under same conditions.

Adolescent↗