Spiroarsoranes, a new class of antiparasitical compounds: quantitative analysis by high-performance liquid chromatography.
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Animals↗
Biomedical subjects
G Houin
Publications and source records attributed to G Houin.
Quantitative determination of alizapride in human plasma by high-performance liquid chromatography.
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Anti-Arrhythmia Agents↗
Influence of bile salts and lipids on intestinal absorption of griseofulvin in man.
The influence of bile salts and lipids on the intestinal absorption of griseofulvin has been studied in 11 healthy male volunteers by the intestinal perfusion technique. The drug in a nutrient solution (Realmentyl) was perfused into the second part of duodenum at 5 ml/min. Intestinal samples were taken continuously at 1 ml/min, 20 cm (at the angle of Treitz) and 45 cm distal to the perfusion point. To study the effect of lipids on griseofulvin absorption, the drug was perfused with solutions A and B, of which B contained a total lipid and caloric load three times that of A. The influence of bile salts on griseofulvin absorption was examined by perfusing the drug on Day 1 with bile salts and again on the following day after bile salt depletion. Bile salts and a varying quantity of lipid perfusate had no significant influence on the duodeno-jejunal griseofulvin absorption rate per cm of intestine. Lipids, however, may still play a role in griseofulvin absorption along the entire intestine.
Adult↗
Pharmacokinetics and bioavailability of ranitidine in normal subjects and cirrhotic patients.
Pharmacokinetic parameters of ranitidine were determined comparatively in nine cirrhotic patients and eight healthy volunteers after administration of a single oral (150 mg) or intravenous dose (50 mg). Bioavailability was virtually the same in patients and in normal subjects, and there was no significant difference between the two groups for total plasma clearance, intravenous elimination half-life, or volume of distribution. The mean maximum plasma concentration was 43% higher in patients than in volunteers, but the difference was not significant. The values for the kinetic parameters did not significantly differ between patients with and without ascites or with and without hepatocellular insufficiency. These results indicate that ranitidine kinetics are not appreciably altered in cirrhotic patients and that reduction of dosage is not required in such patients unless their renal function is impaired.
Adult↗
In vitro binding study of gemfibrozil to human serum proteins and erythrocytes: interactions with other drugs.
The binding of gemfibrozil to human serum, isolated proteins and erythrocytes was studied in vitro by equilibrium dialysis. Our results show that this drug is highly bound to serum (99%) at therapeutic levels. Human serum albumin was shown to be mainly responsible for this binding (98.6%) with a saturable process characterized by two binding sites with a moderate affinity. Like many acidic drugs with a carboxylic acidic group, gemfibrozil showed none or negligible binding to alpha 1 acid glycoprotein, lipoproteins and gamma-globulins. The drug binding to erythrocytes is very low (0.8%). The unbound fraction in blood remains constant (0.8%) within the range of therapeutic concentrations. Moreover, interactions were studied with bilirubin and palmitic acid at pathophysiological concentrations and acenocoumarol, salicylic acid, valproic acid, furosemide, phenylbutazone, tolbutamide, warfarin and sulfamethoxazol at therapeutic concentrations. Neither endogenous compounds nor the other drugs studied altered gemfibrozil binding in serum. Likewise, the binding of warfarin to serum and to human serum albumin (600 microM) is not influenced by gemfibrozil.
Blood Proteins↗
Pharmacokinetics of warfarin in the nephrotic syndrome and effect on vitamin K-dependent clotting factors.
The behavior of warfarin, a drug tightly bound to albumin, was studied in patients with nephrotic syndrome (NS) to assess the influence of hypoalbuminemia on its pharmacokinetics and its effect on vitamin K-dependent coagulation factors. A single dose of warfarin (8 mg) was given orally to 11 nephrotic patients with normal or nearly normal renal function and to 11 controls. In every subject the following measurements were performed: albuminemia before (t0) warfarin administration; plasma warfarin and vitamin K-dependent coagulation factors (FII, FVII, FIX, FX) levels, before and at time intervals from 0 to 48 h after drug administration; warfarin urinary excretion from 0 to 24 h. Urinary warfarin excretion was null in 19 out of the 22 subjects and very low in two nephrotic patients and in one control. Low serum albumin in NS patients induced a twofold increase of unbound warfarin vs controls (3.5% vs 1.8%, p less than 0.001) which led to a threefold increase in plasma clearance of warfarin (9.70 vs 3.26 ml X min-1, p less than 0.001); as warfarin distribution volume showed only a slight (non significant) increase in NS patients, the elimination half-life was thus markedly shortened in NS patients vs controls (18 vs 36 h, p less than 0.01). Maximum warfarin effect on vitamin K-dependent factor levels occurred at 18 h in controls and 24 h in nephrotics, and these lowest values were similar, in spite of a higher level at 0 in NS patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Binding of bornaprolol to human serum proteins and blood cells.
The binding of 14C-bornaprolol to human serum proteins and to blood cells and platelets was studied by equilibrium dialysis and centrifugation. Bornaprolol binding to alpha 1-acid glycoprotein (n = 1.89, K = 433,900 M-1) was found to be a saturable phenomenon. By contrast, a non-saturable binding was observed with serum albumin (nK = 6.4 X 10(3) M-1), HDL (nK = 205 X 10(3) M-1), LDL (nK = 1,530 X 10(3) M-1), VLDL (nK = 2,342 X 10(3) M-1) and gamma globulins (nK = 25 X 10(3) M-1). The binding to blood cells was negligible. All the binding parameters were used to simulate the distribution of bornaprolol between serum proteins and blood cells over the range of therapeutic concentrations and showed that serum albumin, red blood cells and alpha 1 acid glycoprotein were the major binding components.
Blood Cells↗
Pharmacokinetics and bioavailability of doxycycline in humans.
The bioavailability of a new tablet of 6-deoxy-5-hydroxytetracycline (doxycycline, Doxycline Plantier) was estimated relatively to an oral solution and a commercially available capsule. Each form was administered to 12 healthy volunteers according to a replicated latin square. Statistical analysis of non-compartmental pharmacokinetic parameters - maximum concentrations, corresponding time, area under the plasma concentrations curve and unchanged amounts recovered in the urine - failed to show any difference between the tested pharmaceutical forms, although the new tablet allows to reach higher concentrations.
Adult↗
Binding of minaprine to human serum proteins and erythrocytes.
The binding of minaprine to human serum, isolated proteins and erythrocytes was studied in vitro. This drug shows both a saturable and a nonsaturable binding process in serum. The drug is bound to alpha 1-acid glycoprotein in a saturable fashion with a moderate affinity whereas albumin is involved in the nonsaturable and major binding. The combination of these two processes results in a slight decrease (7%) in the drug binding to serum within the range of therapeutic concentrations. Competitive binding with metabolites of minaprine or with other basic drugs seems unlikely when these compounds are present in serum at therapeutic levels. The binding of minaprine to erythrocytes remains constant within the range of therapeutic concentrations.
Blood Proteins↗
Diclofenac binding to albumin and lipoproteins in human serum.
The binding of diclofenac to human serum albumin (HSA) and to lipoproteins was studied in vitro by equilibrium dialysis. Binding to HSA is characterized by two classes of sites with one site each (K1 = 5 X 10(5) M-1 and K2 = 0.6 X 10(5) M-1). The binding to lipoproteins was shown to be saturable with a larger number of binding sites and low association constants. The evidence of two specific binding sites on HSA was confirmed by circular dichroism data. In addition, an identification of those sites was performed by displacement of fluorescent probes. The data show that the high affinity site (K1 = 5 X 10(5) M-1) is likely to be shared by benzodiazepines while the second one (K2 = 0.6 X 10(5) M-1) is common with the warfarin site.
Binding Sites↗
Primary dose-dependent pharmacokinetic study of veralipride.
A dose-dependent pharmacokinetic study of veralipride (a new post-menopausal "hot flushes" regulator) was developed in humans after oral solution administration (100, 150, 200, and 250 mg). In most cases, two maxima of plasma drug concentrations occurred, probably due to a double intestinal site of absorption. From model independent pharmacokinetic parameters, it can be concluded that a linearity in the tested range doses exists.
Adult↗
Protein binding of propisomide.
This paper describes the protein binding of propisomide to human serum and isolated proteins using equilibrium dialysis. The drug is exclusively bound to alpha1-acid glycoprotein with high affinity. The binding is saturable even at low concentrations of the drug. Thus, the fraction unbound varied from 0.05 to 0.60 with decreasing serum concentration. The major metabolite of the drug or other drugs with affinity for alpha1-acid glycoprotein can displace propisomide from its binding site only when present in serum at high levels. Two ultrafiltration techniques are compared to equilibrium dialysis for the determination of serum protein binding of propisomide. Ultrafiltration does not give reliable results. Equilibrium dialysis is retained as an accurate method for the determination of the fraction unbound of propisomide.
Adult↗
Equilibrium dialysis, ultrafiltration, and ultracentrifugation compared for determining the plasma-protein-binding characteristics of valproic acid.
Equilibrium dialysis, ultrafiltration, and ultracentrifugation were compared to determine their reliability and applicability in the study of binding of an anticonvulsant drug, valproic acid, by plasma proteins. We studied drug binding with pooled serum and with solutions of human serum albumin at physiological concentrations. We compared binding characteristics such as number of binding sites, affinity constants, and percent of binding as measured by each method in the therapeutic range for valproic acid. Results by ultracentrifugation differed from those by equilibrium dialysis and ultrafiltration, which agreed reasonably well with each other.
Blood Proteins↗
Liquid-chromatographic determination of propisomide and its mono-N-dealkylated metabolite in plasma and urine.
We describe a "high-performance" liquid-chromatographic assay for simultaneously determining propisomide and its mono-N-dealkylated metabolite in plasma and urine. After extraction with dichloromethane at alkaline pH, the unchanged drug, its metabolite, and the internal standard are separated by liquid chromatography on a reversed-phase column and the absorbance of the eluate is measured at 254 nm. Selectivity, sensitivity, and reproducibility are excellent. Results are similar to those by gas chromatography for propisomide but, in addition, the metabolite can be simultaneously measured in the same clinical sample. We also report results by this method for blood and plasma samples from a volunteer receiving a single 200-mg dose of propisomide.
Anti-Arrhythmia Agents↗
Dose-dependent pharmacokinetic study of pefloxacin, a new antibacterial agent, in humans.
A dose-dependent pharmacokinetic study of pefloxacin was performed after four intravenous infusions and four orally administered doses. After intravenous infusion, the pharmacokinetic profiles of the plasma concentrations showed a biphasic decline, with half-lives (mean +/- SD) of 8.55 +/- 4.20 min and 11.50 +/- 1.75 h, respectively. Intravenous infusion and oral administration yielded similar results. The pharmacokinetic parameters remained constant in the dose range of 200-800 mg from the plasma and urine data.
Administration, Oral↗
Absolute intramuscular, oral, and rectal bioavailability of alizapride.
A study was designed to estimate the absolute bioavailability of alizapride after intramuscular injection, oral administration as a solution or a tablet, and rectal administration as a suppository compared with that after intravenous injection. A balanced incomplete block-design trial was adopted. The intramuscular injection and the tablet administration showed identical results with those of the intravenous injection. On the contrary, the oral solution and the rectal suppository dosage forms gave lower absorption values, i.e., 75 and 61% of the dose administered was absorbed, respectively.
Administration, Oral↗
Influence of food on the absorption of the p-chlorophenolic ester of chlorophenoxyisobutyric acid in man.
A study was designed to investigate the effect of a fatty meal on the absorption of chlorophenoxyisobutyric acid (CPIB) in six healthy adult volunteers after oral administration of the p-chlorophenolic (PCP) ester of CPIB. Plasma concentrations of CPIB when administered with food were higher than those observed in the fasting state. The Cmax in the former case was 24.0 +/- 4.6 mg l-1 as against a value of 15.2 +/- 6.9 mg l-1 in the latter (P less than 0.01). The pharmacokinetic parameters measured were found to be linear with the dose administered. This could be due to low plasma concentrations of CPIB unable to cause a saturation of the plasma protein binding of this drug. It is concluded that a fatty meal enhances the absorption of this hypolipidaemic drug.
Adult↗
Decreased alpha 1-acid glycoprotein in liver cirrhosis: consequences for drug protein binding.
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Adult↗