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Biomedical subjects

E Singlas

Publications and source records attributed to E Singlas.

At least 55 records · Page 3Linked to original sources
PubMed1987

Pharmacokinetics of ciprofloxacin tablets in renal failure; influence of haemodialysis.

The pharmacokinetics of ciprofloxacin has been studied after a single oral dose of 500 mg given to 5 normal subjects (N) and to 15 patients grouped according to their residual renal creatinine clearance: Group I, 8-30 ml X min-1, Group II, less than 8 ml X min-1, and Group III, haemodialysed patients studied twice--during an interdialysis period (IIIa) and in a 4 h haemodialysis session (IIIb). Ciprofloxacin was assayed by reverse phase HPLC using a spectrofluorimetric detection. The peak plasma concentration (2-5 mg X l-1) was reached within 2 h after drug administration. Apparent volume of distribution, 6.6 (N), 5.0 (I), 2.7 (II) and 4.2 (IIIa) l X kg-1 and total plasma clearance, 770 (N), 440 (I), 378 (II) and 314 (IIIa) ml X min-1 were decreased in relation to the degree of renal impairment. Mean plasma half-lives for patients in the 4 groups were 7.3 (N), 10.4 (I), 7.2 (II) and 9.3 (IIIa) h. In groups N, I and II, 40, 16 and 8% of the administered dose was eliminated through the kidney, with mean renal clearances of 305 +/- 63, 61 +/- 21 and 21 +/- 3 ml X min-1. A linear relationship was found between the renal clearance of ciprofloxacin and the glomerular filtration rate (r = 0.75, n = 15). Ciprofloxacin was partly removed by haemodialysis (IIIb): the dialyser extraction ratio was 23% and the dialysis clearance was 40 ml X min-1.

Administration, Oral↗
PubMed1987

Penetration of ciprofloxacin into cerebrospinal fluid of patients with bacterial meningitis.

We evaluated the diffusion of ciprofloxacin into the cerebrospinal fluid (CSF) in 23 patients with bacterial meningitis or ventriculitis undergoing treatment with other antibiotics. Three successive ciprofloxacin doses of 200 mg were administered intravenously at 12-h intervals, first between days 2 and 4 and again between days 10 and 20 after the admission. Concentrations of ciprofloxacin in plasma and CSF obtained at 60, 120, 240, and 480 min after the third infusion were determined by high-performance liquid chromatography. In addition, serial samples were obtained from ventricular fluid in four patients. The concentrations of ciprofloxacin in CSF ranged from 0.35 to 0.56 micrograms/ml. These concentrations were equal to or higher than the MICs for most of the enterobacteria.

Adult↗
PubMed1986

Pharmacokinetics of ornidazole in patients with severe liver cirrhosis.

Pharmacokinetics of ornidazole, a nitroimidazole derivative, was studied after intravenous injection in 10 patients with severe alcoholic cirrhosis and 10 healthy volunteers. Plasma concentrations of ornidazole and its two major hydroxylated metabolites, M1 (alpha-(chloromethyl)-2-hydroxymethyl-5-nitroimidazole-1-ethanol) and M4 (3-(2-methyl-5-nitroimidazole 1-yl) 1,2 propane diol), were measured by HPLC. The t1/2 of ornidazole was 14.1 +/- 0.5 hours for normal subjects and 21.9 +/- 2.9 hours for patients with cirrhosis. Mean plasma clearance was 50.6 +/- 2.1 ml/min in control subjects and 34.9 +/- 4.9 ml/min in patients, whereas apparent V SS was not modified in hepatic insufficiency. In healthy volunteers, M1 and M4 levels are well below levels of the parent drug; in cirrhosis both metabolites accumulate in plasma as a result of decreased elimination. Hepatic cirrhosis prolongs ornidazole elimination, and to avoid cumulation the interval between repeated doses could be doubled.

Adult↗
PubMed1985

[Metabolism and pharmacokinetics of atracurium].

Atracurium is a new neuromuscular blocking agent which has an unique mode of elimination by spontaneous degradation in slightly alkali solution, according to the Hofmann elimination. The Hofmann elimination is completed in plasma (in vitro or in vivo) by an ester hydrolysis. The major degradation product is laudanosine. Metabolites can be considered as pharmacologically inactive with the usual doses of atracurium. Spontaneous degradation of atracurium in plasma is the major route of elimination in man and contributes to a short elimination half-life (approximatively 20 min). Distribution half-life is short and central and peripheral volumes are small when compared with the usual neuromuscular blocking agents. The pharmacokinetic parameters give a rapid dynamic equilibrium so that incremental doses will not lead to accumulation phenomenon. Because of spontaneous degradation of atracurium in plasma, its kinetics are theoretically independent of renal and liver functions. Only a slight increase of distribution volumes can be seen in very severe renal/hepatic failure. Atracurium pharmacokinetics could theoretically be modified by some modifications of acid-base equilibrium or alterations of thermoregulation. Pharmacokinetic studies are not yet available in these areas.

Acidosis↗
PubMed1985

Pharmacokinetics of ornidazole in patients with renal insufficiency; influence of haemodialysis and peritoneal dialysis.

The pharmacokinetics of ornidazole (Tiberal) was studied after intravenous administration of a single 500 mg dose in eight patients with advanced chronic renal failure (ACRF) (creatinine clearance 2-16 ml/min), in seven patients treated by haemodialysis (residual renal creatinine clearance 0-5 ml/min) and in five patients treated by continuous ambulatory peritoneal dialysis (CAPD) (residual renal creatinine clearance 0-6 ml/min). In ACRF patients, the half-life of ornidazole was 10.8 +/- 1.4 h, the total plasma clearance 46.3 +/- 2.3 ml/min and the volume of distribution 0.73 +/- 0.06 l/kg. During haemodialysis, ornidazole was partly removed: the dialyser extraction ratio was 42 +/- 5% and the dialysis clearance 64 +/- 7 ml/min. During CAPD, peritoneal excretion was low: the dialysis clearance was 3.0 +/- 0.4 ml/min and in 48 h 6.0 +/- 1.1% of the administered dose was found in the peritoneal fluids. In these patients, the half-life of ornidazole was 11.8 +/- 0.8 h and total plasma clearance was 48.3 +/- 5.5 ml/min, values which were close to those determined in non dialysed patients. In patients with end-stage renal disease, the half-life of ornidazole is comparable to that of subjects with normal renal function. This is due to the predominantly extra-renal elimination of the drug. Therefore, there is no need to modify the usual dosage of ornidazole for these patients. Because of the large elimination of the drug during haemodialysis it is necessary to administer the drug after the dialysis session.

Adult↗
PubMed1985

Haemodialysis does not affect the pharmacokinetics of nifedipine.

To establish dosage recommendations in patients with end-stage renal disease undergoing chronic haemodialysis, nifedipine kinetics were studied between and during haemodialysis sessions. In eight patients, during the interdialytic period, peak plasma concentrations of nifedipine (29-332 ng/ml) were reached 0.5-1.0 h after administration of a single 10 mg oral dose. Elimination half-life and oral plasma clearance were respectively 2.6 +/- 0.5 h and 1 176 +/- 412 ml/min. Nifedipine plasma protein binding was decreased in uraemic patients (88.8 +/- 0.3% vs 94.4 +/- 0.1%) but not affected by haemodialysis. Removal by haemodialysis was low: the dialyser extraction ratio and the dialysis clearance were respectively 2.3 +/- 0.8% and 2.8 +/- 0.9 ml/min.

Adult↗
PubMed1985

[Clinical pharmacology of calcium inhibitors].

The pharmacokinetics of the commercially available calcium antagonists, diltiazem (Tildiem), nifedipine (Adalate), perhexiline (Pexid), and verapamil (Isoptine) are well known; the pharmacokinetics of bepridil (Cordium) need further study. The properties of nicarpidine, a molecule currently being tested, will also be described. These products are well absorbed from the gastrointestinal tract but undergo variable degrees of transformation during the first passage through the liver. The bioavailabilities of bepridil, diltiazem and nifedipine are of the order of 40 to 60%; those of verapamil and nicarpidine are lower, 10-20% and 15-30%, respectively. The rates of absorption vary according to the derivatives and galenic preparations; in general, they are rapid; peak plasma concentrations are usually obtained one to four hours after administration. Protein binding is high but does not interfere in the distribution; the volumes of distribution of bepridil, diltiazem and verapamil are large (4-5 l/kg); those of nifedipine and nicardipine are smaller (l l/kg). The halflives of diltiazem, nifedipine, nicardipine and verapamil are short (1 to 5 hours); those of bepridil and perhexiline are longer (2 to 3 days). The main method of elimination is by hepatic transformation with high plasma clearance rates: diltiazem and verapamil have pharmacologically active derivatives whose contributions to the overall activities of the drugs are not fully understood. Physiopathological changes of the pharmacokinetic properties of diltiazem and verapamil (elderly patients, hepatic failure) have been described.

Age Factors↗
PubMed1985

Diuretic effect and pharmacokinetic data observed at different stages of chronic renal failure with 240 mg of muzolimine.

Muzolimine (240 mg) was administered orally to 24 patients with chronic renal failure. In five patients with creatinine clearance ranging between 10 and 30 ml/min and five others with creatinine clearance lower than 10 ml/min, urinary output was measured in periods of 24 hours before, and 0 to 4, 4 to 10, 10 to 24, 24 to 48, 48 to 72 hours after administration of the drug. The amounts of sodium, chloride, potassium and urea excreted in each sample were determined. Our results show that the diuretic activity of muzolimine 240 mg in these patients is excellent, especially in the first four hours after its administration. Pharmacokinetic data observed in advanced renal failure (creatinine clearance between 10 and 30 ml/min) are similar to those observed in healthy subjects or patients with normal renal function. However, attention should be paid to possible accumulation of the drug in terminal renal failure (creatinine clearance lower than 10 ml/min) because a significant increase of the terminal half-life of the drug is observed in these patients. Dialysibility of the drug in haemodialysis and during chronic ambulatory peritoneal dialysis is poor.

Adult↗
PubMed1984

[Clinical pharmacokinetics of almitrine dimesylate].

In healthy subjects, almitrine bismesylate taken orally as tablets is rapidly absorbed from the digestive tract, with an overall bioavailability of about 70%. Drug kinetics are linear and independent of route of administration and therapeutic doses. Protein binding is approximately 99%, irrespective of plasma concentrations. Wide diffusion through body tissues is reflected in the apparent volume of distribution approaching 15 l/kg. In all animal species studied, almitrine is primarily metabolized in the liver. Its main metabolites are the tetrahydroxyl, mono-deallyl, di-deallyl and detriazinyl derivatives, all devoid of pharmacological activity and excreted mostly through the bile. Plasma elimination half-life varies from 45 to 50 hours. Plasma clearance (4 ml/min/kg) is about the same as hepatic clearance. As compared with healthy subjects, the pharmacokinetic values of almitrine bismesylate are identical in patients with chronic respiratory failure and not significantly different (notably with regard plasma clearance) in patients with renal impairment. However, absorption may be normal, reduced or delayed in patients with impaired liver functions, resulting in more variable values. Following repeated administration of the drug to healthy volunteers, steady state is reached in about 15 days. In chronic obstructive lung disease, long-term oral administration of almitrine bismesylate 100 mg/day divided into two 50 mg doses results in plasma concentrations that are 2 to 3 times higher than after one single 100 mg dose.

Adult↗
PubMed1984

[Clinical pharmacokinetics of azlocillin].

The pharmacokinetics of azlocillin have been studied in healthy subjects and in patients, in children and in adults, using different doses, either single or repeated. Following intravenous injection of doses ranging from 1 to 5 g, plasma concentrations increase in relation to dosage. Maximum concentrations at the end of an injection or infusion average 100-200 micrograms/ml with 1 g and 400-500 micrograms/ml with 5 g. Azlocillin has a low degree of plasma protein binding: 30% to 40% depending on concentrations. Its volume of distribution is approximately 0.2 l/kg. Tissue distribution has been studied by various authors: with a 2 to 5 g dose, therapeutically active concentrations have been found in a variety of tissues, including bronchial secretions, bone, etc. Azlocillin crosses the placenta; the ratio of maternal to foetal plasma concentrations is 0.50. Azlocillin undergoes little metabolic degradation and its metabolites (penicilloates) amount to less than 15% of the dose administered. Most of the drug is excreted by the kidneys, 50% to 70% of the dose injected being recovered in the 24 h urines; the remainder is excreted in the bile, and biliary concentrations may be as high as 15-fold the corresponding plasma concentrations. Azlocillin is rapidly cleared. Its plasma half-life varies from 45 to 75 min according to different authors. The fact that it increases slightly with dosage suggests the kinetics of the drug might be dose-dependent. In view of the intervals between doses, this is certainly not of therapeutic importance. Total and renal clearance values are 150-200 ml/min and 100-140 ml/min respectively. In patients with renal impairment azlocillin is eliminated more slowly, with a half-life of up to 6-10 h when creatinine clearance is below 5 ml/min. The reduced urinary excretion may partly be compensated for by increased biliary excretion. The proportion of drug removed by haemodialysis is 40-50%. Azlocillin excretion is slowed down in children under 3 months of age, with half-lives of 4.5 h, 3.0 h and 2.0 h respectively in prematures, neonates and infants.

Azlocillin↗
PubMed1983

Acute antihypertensive effect and pharmacokinetics of a tablet preparation of nifedipine.

A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (-18%) and lasted longer (12 h) after 60 mg than after 20 mg (-11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration--time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r = 0.61, p less than 0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.

Adult↗
PubMed1983

Moxalactam kinetics during chronic ambulatory peritoneal dialysis.

Moxalactam kinetics in renal failure were followed in eight patients undergoing chronic ambulatory peritoneal dialysis (CAPD) after a single 1-gm IV infusion. Elimination t 1/2 was 16.7 +/- 2.1 hr, with an apparent volume of distribution of 0.21 +/- 0.01 l/kg and plasma clearance of 10.6 +/- 2 ml/min. In 24 hr, 17.4 +/- 3.1% of the dose was present in the dialysis fluids, and 14.6 +/- 5.7% was excreted in the urine. Renal and peritoneal clearance values were thus 2.3 +/- 1.1 and 2.7 +/- 0.5 ml/min. Peritoneal concentrations were high (22.7 +/- 2.2 micrograms/ml). A recommended dosage schedule is proposed on the basis of moxalactam kinetics during CAPD.

Adult↗
PubMed1983

[Benzodiazepines. Factors altering pharmacokinetic parameters and drug interactions].

Drug level at receptor site dictates the intensity of the pharmacological response. The level which is achieved depends upon several factors such as gastrointestinal absorption, protein binding, distribution, biotransformations and excretion. Modification of anyone of these processes can influence drug level at the site of action and thus the therapeutic effect of the drug. Physiological and pathological states or drug interactions can influence pharmacokinetics of benzodiazepines and thus modification of dosage regimen may be necessary. The influence of aging, liver disease, drug interactions such as alcohol, antidepressants... is of importance. Consequences of these modifications are discussed.

Adolescent↗