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R Gomeni

Publications and source records attributed to R Gomeni.

At least 37 records · Page 2Linked to original sources
PubMed1994

Pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis.

BACKGROUND: Rocuronium, like other steroidal nondepolarizing muscle relaxants, may in part be eliminated by the liver. To determine the influence of liver disease on its neuromuscular blocking effect, we studied the pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis. METHODS: Eighteen patients undergoing elective surgery, 10 with cirrhosis and 8 with normal liver function, were studied. Anesthesia was induced with intravenous thiopental 5-7 mg.kg-1 and maintained with 60% nitrous oxide in oxygen and repeated doses of fentanyl 2 micrograms.kg-1. The force of thumb adduction in response to supramaximal ulnar nerve stimulation was monitored and recorded. An intravenous bolus of rocuronium 0.6 mg.kg-1 was administered and venous blood sampled at frequent intervals for 6 h. Plasma concentrations of rocuronium was measured by high-pressure liquid chromatography. Data were fitted to both a pharmacokinetic and a pharmacodynamic model by using a two-compartment open model and an effect compartment model. Data were analyzed by least-squares regression. RESULTS: The onset of neuromuscular blockade was longer (P < 0.01) in patients with cirrhosis (158 +/- 56 s) than in normal patients (108 +/- 33 s). Recovery of the thumb twitch to 75 and 90% of its control value was 77 +/- 25 and 88 +/- 29 min in cirrhotic patients versus 57 +/- 11 and 64 +/- 13 min, respectively, in normal patients (P < 0.05). The central volume of distribution of rocuronium was 104 +/- 21 in cirrhotic patients and 78 +/- 24 ml.kg-1 in normal patients (P < 0.05). No significant difference in elimination kinetics was observed between the two groups. The elimination half-life was 87.5 +/- 17.5 min in normal patients and 96.0 +/- 36.8 min in cirrhotic patients (difference not significant). This increased onset time was linearly correlated to the increased central volume of distribution of rocuronium in cirrhosis. CONCLUSION: Rocuronium onset time is longer in cirrhotic patients than in those with normal liver function; this can be explained by an increase in the volume in which rocuronium initially distributes. Although elimination kinetics are unchanged in patients with cirrhosis, rocuronium recovery time is prolonged in cirrhotic patients.

Androstanols↗
PubMed1993

A Weibull distribution model for intradermal administration of ceftazidime.

The pharmacokinetics of 1 g of ceftazidime administered intradermally was studied in seven healthy volunteers. The objective of the present study was to find the most appropriate mathematical model to describe the drug intake process. The concentration of ceftazidime in plasma was measured by HPLC. The disposition of the drug was described by a one-compartment pharmacokinetic model, with drug intake occurring by different processes: a zero-order process due to the administration and a first-order intake from the injection site to the systemic circulation. The Weibull model was considered as an approximation of the overall process. The mean Weibull parameters were td (time necessary to transfer 63% of the administered drug into the systemic circulation) of 2.75 +/- 0.75 h, and f (shape) of 1.04 +/- 0.15. The mean elimination half-life was 2.0 +/- 0.4 h. The area under the concentration versus time curve obtained in this study (139 +/- 46 mg.h/L) is very near to literature values reported after single intravenous doses of 1 g of ceftazidime, suggesting that the bioavailability of ceftazidime after intradermal administration may be approximately 100%. Moreover, the mean peak plasma concentration (37 +/- 16 mg/L) is in the same range as that reported in the literature after intramuscular administration of a single dose of 1 g.

Administration, Cutaneous↗
PubMed1993

Multiple-dose pharmacokinetics of pefloxacin in patients with hepatocellular deficiency.

Multiple-dose pharmacokinetics of pefloxacin were evaluated in 25 patients with hepatocellular insufficiency. The severity of liver disease was graded A, B or C according to the Child-Pugh classification. Pharmacokinetic parameters evaluated in patients on day 1 of treatment were compared with those computed in 11 healthy volunteers (the control group) after a single dose. Blood samples were taken at frequent intervals after drug administration and assayed by high performance liquid chromatography. The mean age of patients with liver impairment was slightly greater (59.5 years, range 33 to 81 years) than that of the control group (46.7 years, range 42 to 51 years). In the patients with liver disease, the mean (+/- SD) half-life of elimination, although highly variable, was significantly longer (46.3 +/- 42.5 hours) than in the control group (11.3 +/- 3.5 hours, p < 0.001). The total clearance was significantly decreased (1.76 +/- 1.31 L/h vs 6.03 +/- 2.99 L/h in the control group). In groups B and C of the Child-Pugh classification, total body clearance was about 30% of normal values. Elimination half-life increased by 200% in group B and 373% in group C compared with values in healthy volunteers. Intergroup differences (group B vs group C of the Child-Pugh classification) were not statistically significant. The minimum concentrations inhibiting 90% of Gram-negative strains (MIC90) were exceeded by plasma pefloxacin concentrations throughout treatment. For most patients, trough plasma concentrations were above 2 mg/L and peak plasma concentrations averaged 8.5 mg/L. Large inter- and intraindividual variations in the elimination half-life, total clearance and volume of distribution were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Endotracheal and aerosol administrations of ceftazidime in patients with nosocomial pneumonia: pharmacokinetics and absolute bioavailability.

Pharmacokinetic studies on ceftazidime, an aminothiazole cephalosporin with a wide spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa, were performed in patients with nosocomial pneumonia. The concentration-time profiles of ceftazidime in plasma, urine, and bronchial secretions of 12 patients were investigated after intravenous (i.v.) (n = 12), endotracheal (n = 10), and aerosol (n = 5) administrations. In all cases a 1-g dose was administered. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection. The elimination of the drug from the blood followed a biexponential (i.v. administration) or a monoexponential (endotracheal and aerosol administrations) decay, with an elimination half-life of 6 h and a total body clearance of 4.2 liters/h. The apparent volume of distribution was 0.36 liter/kg of body weight. Renal clearance of the drug accounted for 58% of the total clearance; 66% +/- 17.7%, 33.5% +/- 17.3%, and 6.59% +/- 3.45% of the administered dose were eliminated in urine as parent drug after i.v., endotracheal, and aerosol administrations, respectively. The absolute bioavailabilities were 0.47 and 0.08 for endotracheal and aerosol administrations, respectively. Very high concentrations were found in bronchial secretions after local administration. The MICs for 90% of the most important pathogens responsible for nosocomial infections were exceeded by concentrations in bronchial secretion for up to 12 h after i.v. infusion and for up to 24 h after endotracheal and aerosol administrations.

Adult↗
PubMed1991

Steady-state pharmacokinetics of ciprofloxacin in plasma from patients with nosocomial pneumonia: penetration of the bronchial mucosa.

A 30-min intravenous (i.v.) infusion of 200 mg of ciprofloxacin was administered twice daily to 12 patients with nosocomial pneumonia scheduled to undergo diagnostic fiberoptic bronchoscopy. The pharmacokinetics of ciprofloxacin were examined at the presumed steady state after 5 days of treatment. Eleven successive plasma samples were collected in the interval from 0 to 12 h after administration, and bronchial mucosa samples were taken 2 h after administration. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with fluorimetric detection. The results showed that the kinetics in plasma did not differ from those determined previously in healthy volunteers. The mean concentrations in plasma peaked at 4.94 +/- 2.90 mg/liter at the end of infusion. The terminal half-life was 4.95 +/- 2.81 h, and the mean residence time 6.13 +/- 3.17 h. A large volume of distribution was calculated: 2.59 +/- 1.43 liters/kg. Mean total body clearance was 23.3 +/- 10.1 liters/h. The concentrations in bronchial mucosa reached 21.6 +/- 5.63 micrograms/g 2 h after drug intake. The tissue-versus-plasma concentration ratios ranged from 10.1 to 26.3 (mean value, 16.9 +/- 5.43). After 6 to 12 days of i.v. treatment, four patients were switched to oral ciprofloxacin. We propose a model for the simultaneous fit of the concentration-time curves obtained after i.v. infusion and oral dosing. The concentrations in tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ciprofloxacin.

Administration, Oral↗
PubMed1990

Estimate of the number and of the temporal sequence of measurements in a kinetic experiment.

The optimal choice of the number and the temporal sequence of measurements is that which minimizes the expected error on the parameters of the model later used to fit the observations. Practical constraints regarding the feasibility of a given temporal distribution of measurements, cost-benefit ratio as well as prior knowledge about the parameters and their variability in the selected population must be integrated in the decisional process. A non-linear integer programming procedure is used to find reasonable solutions to this problem.

Models, Biological↗
PubMed1987

OMNE: a new robust membership-set estimator for the parameters of nonlinear models.

A new method for estimating parameters and their uncertainty is presented. Data are assumed to be corrupted by a noise whose statistical properties are unknown but for which bounds are available at each sampling time. The method estimates the set of all parameter vectors consistent with this hypothesis. Its results are compared with those of the weighted least squares, extended least squares, and biweight robust regression approaches on two data sets, one of which includes 33% outliers. On the basis of these preliminary results, the new method appears to have attractive properties of reliability and robustness.

Kinetics↗
PubMed1987

Plasma and brain pharmacokinetics of mianserin after single and multiple dosing in mice.

Pharmacokinetics parameters describing the time course of concentrations of mianserin (MIA) in plasma and brain and the relationship between plasma and brain concentrations were studied after acute and chronic administration of increasing doses of MIA in adult mice. There was a linear relationship between the area under the curve (AUC), the maximum concentration (Cmax) and doses, in plasma and brain, both during acute and chronic experiments (p less than 0.05). A five-fold variation in plasma and brain terminal half-life (t 1/2) after chronic administration of the drug was observed, possibly due to a reduction in plasma drug clearance (CL). The values of Cmax and AUC in plasma and brain showed an increase of respectively about three and twelve times after chronic treatment. A very good correlation was observed between plasma and brain Cmax in both acute and chronic experiments; brain Cmax was 10.2 (+/- 0.16) times higher than plasma Cmax after acute administration and 12.08 (+/- 1.33) times higher after chronic administration.

Animals↗
PubMed1987

Systemic and regional hemodynamic characterization of alpha-1 and alpha-2 adrenoceptor agonists in pithed rats.

In pithed rats, blood pressure dose-response curves to i.v. cirazoline, methoxamine and phenylephrine (full alpha-1 adrenoceptor agonists) exhibited higher maxima than those to B-HT 920, M-7, UK-14,304 (full alpha-2 adrenoceptor agonists) and indanidine (Sgd 101/75: partial alpha-1 adrenoceptor agonist). For an 80 mm Hg increase in blood pressure, full alpha-1 adrenoceptor agonists enhanced total peripheral, renal and mesenteric vascular resistances significantly more than alpha-2 adrenoceptor stimulants or indanidine. In contrast, all compounds produced a similar degree of hindquarter vasoconstriction, suggesting that both types of alpha adrenoceptors have the same functional importance in this skeletal muscle vascular bed. Application of a multivariate discriminant analysis to the drug-induced changes in the total peripheral and mesenteric vascular resistances associated with a pressor effect of 80 mm Hg allowed their assignment to two distinct groups corresponding to the full alpha-1 and the full alpha-2 adrenoceptor agonists plus indanidine. All investigated compounds in low doses increased cardiac output, which returned to base-line values after high doses of alpha-1 but plateaued after high doses of alpha-2 adrenoceptor agonists or indanidine. alpha-1 adrenoceptor agonists decreased whereas alpha-2 stimulants and indanidine successively increased and then decreased renal blood flow. Finally, all investigated compounds increased hindquarter blood flow at low doses but decreased it at high doses. The ratios of the doses of cirazoline required to produce a 100% rise in systemic and local vascular resistances in the presence or in the absence of prazosin were of similar magnitude. This was also true for M-7 when studied in the presence or in the absence of yohimbine. These findings suggest pharmacological identity within alpha-1 as well as within alpha-2 adrenoceptor populations in all investigated vascular beds. Finally, the calcium entry blocker diltiazem did not affect the increases in systemic and regional resistances evoked by cirazoline but depressed profoundly the effects of M-7 and indanidine. In conclusion, full alpha-1 and alpha-2 adrenoceptor agonists can be discriminated easily on the basis of their systemic and regional hemodynamics in the pithed rat. That the hemodynamic effects of the partial alpha-1 adrenoceptor agonist indanidine are similar to those of alpha-2 adrenoceptor agonists and susceptible to calcium channel blockade suggests that the alpha-1 adrenoceptors stimulated by this drug have the same coupling modality as alpha-2 adrenoceptors and share with the latter the same functional expression when stimulated.

Adrenergic alpha-Agonists↗
PubMed1985

Pharmacokinetics and pharmacodynamics of vecuronium (ORG NC 45) in patients with cirrhosis.

To evaluate the effect of liver cirrhosis on the pharmacokinetics and the pharmacodynamics of vecuronium, 12 patients with cirrhosis, aged (mean +/- SD) 52 +/- 12 yr, and 14 control patients, 42 +/- 15 yr, undergoing elective surgery under general anesthesia were studied. The simultaneous time courses of the plasma concentration of vecuronium and of the neuromuscular blockade were studied after the administration of a bolus dose of 0.2 mg X kg-1. Vecuronium plasma concentration declined biexponentially in both groups. Vecuronium plasma clearance was reduced significantly (P less than 0.01) from 4.26 +/- 1.38 ml X min-1 X kg-1 in the controls to 2.73 +/- 1.19 ml X min-1 X kg-1 in the patients with cirrhosis. The elimination half-life was 58 +/- 19 min in the controls and was prolonged significantly to 84 +/- 23 min (P less than 0.01) in the patients with cirrhosis. The total apparent volume of distribution was unchanged in patients with cirrhosis (0.253 +/- 0.086 1 X kg-1 vs. 0.246 +/- 0.092 1 X kg-1 in the controls). Cirrhosis caused a prolongation of the neuromuscular blockade induced by vecuronium: the duration of effect from injection to 50% recovery of the twitch height was prolonged by 100% (P less than 0.01) from 62 +/- 16 min in the controls to 130 +/- 52 min in patients with cirrhosis. The recovery rate (TH 25-75) also was prolonged (P less than 0.05) from 21 +/- 7 min in the controls to 44 +/- 18 min in patients with cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Sulpiride pharmacokinetics in humans after intramuscular administration at three dose levels.

Pharmacokinetics of the disinhibitory psychotropic agent sulpiride was investigated in 9 healthy male subjects after intramuscular administrations of 50, 100, and 200 mg in a 3 X 3 Latin square design. Plasma and urine concentrations were measured by HPLC for 36 and 48 h, respectively. The lowest detectable concentration was 10 ng/mL. Plasma concentration versus time and urinary excretion rate versus time curves were consistent with an open two-compartment body model, where mean +/- SD apparent half-lives of the absorption from muscle, lambda 1 distribution, and lambda 2 elimination phases were 6.96 +/- 2.64 min, 0.220 +/- 0.120 h, and 6.74 +/- 2.67 h, respectively. The initial volume of distribution was 0.145 +/- 0.063 L/kg, the steady-state volume of distribution was 0.639 +/- 0.184 L/kg, and the total clearance was 89.8 +/- 22.3 mL/min. The microscopic rate constants were k12 = 2.53 +/- 1.13 h-1, k21 = 0.674 +/- 0.197 h-1, and k10 = 0.635 +/- 0.298 h-1. Comparison of total clearance (89.8 mL/min), renal clearance (83.0 mL/min), and renal clearance of unbound drug (97.6 mL/min, f = 0.15) indicated that sulpiride is mainly excreted unchanged by the renal route, 93.1 +/- 6.6% of the administered dose being recovered unchanged in urine. Statistical evaluation of all the above parameters, determined at the three dosage levels, did not show any variations related to dose; the pharmacokinetics of sulpiride, over the dose range tested, was therefore linear and independent of dose. The two-compartment body model proposed was validated by digital computer simulation on a small digital computer (32K).

Adult↗
PubMed1984

PHARM--an interactive graphic program for individual and population pharmacokinetic parameter estimation.

This paper describes a new computer program PHARM to estimate individual or population pharmacokinetic parameters in nonlinear models. PHARM is an interactive program which uses graphic facilities to display data and results. The structural model can be defined using differential or integrated equations. The user can also define an error model associated with experimental data. The nonlinear mixed effect model is used to estimate the mean population parameters and their interindividual variability. The maximum likelihood and Bayesian criteria are used to estimate simultaneously the error and structural model parameters.

Computers↗
PubMed1984

Effects in man of progabide on prolactin release induced by haloperidol or domperidone.

The effects of progabide, a GABA receptor agonist, on haloperidol-induced and domperidone-induced hyperprolactinaemia have been studied in man. There was a moderate inhibition by progabide of the rise in prolactin after domperidone. No such effect was found after haloperidol. The results support the view that in man, as in animals, GABA agonists have an inhibitory effect on prolactin release, probably at the level of the hypothalamus and anterior pituitary.

Adult↗
PubMed1984

Betaxolol kinetics in hypertensive children with normal and abnormal renal function.

The kinetic and clinical profile of betaxolol--a beta 1-selective blocker with 80% to 90% bioavailability and a 16 to 20 hr t1/2--were studied in ten children aged 5 to 13 yr with chronic renal hypertension and mild to severe renal failure. An IV dose of 20 mg of betaxolol per 1.73 m2 body surface area (BSA) was followed by six daily oral doses. Six patients were maintained on combination therapy and four on betaxolol alone; two of these were newly treated. After the intravenous dose, t1/2 (mean +/- SE) was 19.9 +/- 1.7 hr, total clearance 0.30 +/- 0.03 l/kg/hr, and volume of distribution 8.2 +/- 0.7 l/kg. Clearance adjusted for BSA was 7.9 +/- 0.6 l/hr. The t1/2 correlated linearly to serum creatinine levels. After the last dose, peak concentration was 97.4 +/- 7.6 ng/ml, and t1/2 19.4 +/- 2.7 hr. Betaxolol 24-hr blood levels were twice as high as after the first dose. Blood pressure was reduced in two newly treated patients and two patients on combination therapy; previous responses were maintained in the others. The maximum effect was reached after the first dose and was maintained throughout the study week. Our results indicate that betaxolol disposition in children aged 5 to 13 yr with different degrees of renal failure is of the same order as that in young healthy adults, implying that there may be a higher rate of non-renal clearance. Renal failure-induced modification led to a doubling of the t1/2 in the most severe cases, again as in adult renal patients. There is an antihypertensive effect.

Acute Kidney Injury↗
PubMed1983

Age-related differences in kinetics and side-effects of viloxazine in man and their clinical implications.

Dose kinetics and side effects of viloxazine (VLX) in 16 healthy volunteers (range age 25-90 years) were studied after single oral administration of 200 mg of VLX. Significant differences in peak plasma values (P less than 0.01), t1/2 (P less than 0.01) and Cl/F (P less than 0.05) were found between subjects under 50 and over 60 years. Positive correlations were found between age and peak plasma values (P less than 0.05), age and AUC (P less than 0.01). No correlations were found between age, t1/2 and Cl/F, due to the high interindividual variability in pharmacokinetic profiles. Total reported and observed side effects scores were higher overall in subjects under 50 years than over 60 years and were inversely correlated to AUC (P less than 0.05). Drowsiness was inversely related to the age of subjects (P less than 0.05). Our data support the importance of single dose kinetic studies, particularly for new antidepressants, in relation to age, both to emphasize differences in pharmacokinetic profiles and to predict side effects during chronic treatment.

Adult↗
PubMed1983

Pharmacokinetics of pinazepam in healthy volunteers.

The kinetics of pinazepam were studied in six healthy male volunteers aged between 26 and 31 years. The drug was administered in a single oral dose (10 mg). The concentrations of the parent compound and metabolites were measured in the plasma and urine by gas-chromatographic analysis. Plasma levels of pinazepam were fitted to a two-compartment open model with first order absorption rate using a three-exponential equation. Absorption rate constant and peak plasma levels of pinazepam were 1.36 +/- 0.15 h-1 and 36.8 +/- 5.1 ng/ml respectively. Plasma decay of the drug consisted of an initial rapid elimination phase (alpha = 0.46 +/- 0.06 h-1) followed by a slow one (beta = 0.046 +/- 0.004 h-1). N-desmethyldiazepam was the only metabolite detected in the plasma. Its plasma concentrations were higher than those of the parent compound shortly after administration. Urine was collected for 72 h after dosing. Those specimens contained unconjugate pinazepam and N-desmethyldiazepam and glucuronated oxazepam and 3-OH-pinazepam. Only 0.016% of the pinazepam administered was recovered as unchanged compound in the urine.

Adult↗
PubMed1982

Influence of age on mianserin pharmacokinetics.

The pharmacokinetics of Mianserin (MIA) after acute administration have been studied in nine volunteers, divided into two groups according to age. The subjects were given a single oral dose of 30 mg MIA. The plasma peak time was shorter in the younger subjects than in the older. In general, the concentrations of MIA in the plasma were higher in the older subjects than in the younger, and in the former group there was no relationship between administered dose (mg/kg) and plasma levels. The area under curve, volume of distribution and clearance were significantly different in the two groups. The side effects (both incidence and type) differed in the two groups. There were no significant changes in blood pressure, either supine or standing. The sedative effect was more marked in the young than in the elderly subjects. A relationship between drowsiness and MIA plasma levels was observed only in the younger subjects.

Adult↗