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A Iliadis

Publications and source records attributed to A Iliadis.

At least 55 records · Page 3Linked to original sources
PubMed1989

Population pharmacokinetics of mitoxantrone performed by a NONMEM method.

To date, the pharmacokinetics of mitoxantrone (1,4-dihydroxy-5,8-bis[[2-[(2- hydroxyethyl)amino]ethyl]amino]anthraquinone) has been described either by an open two- or three-compartment model, showing high interindividual variability. In order to evaluate this variability, residual intraindividual variability, and measurement error, we carried out a population study. A sensitive HPLC method allowed analysis of blood samples drawn from 21 patients with breast cancer or acute nonlymphocytic leukemia. Individual data treatment (22 kinetics) using weighted nonlinear least squares regression confirmed the huge interindividual variability whatever the administration protocol of mitoxantrone: bi- or tri-exponential models fitted the data. The NONMEM population method used herein describes all concentration-time curves by a single three-compartment model, considering biphasic kinetics as fragmentary data. Residual intraindividual variability was 21.4%. Population mean values (+/- interindividual SD) of clearance, terminal half-life, and total volume of distribution were, respectively, 23.40 (+/- 10.76) L/h, 46.87 (+/- 12.18) h, and 385.49 (+/- 196.60) L. These results are of particular interest in clinical routines to calculate dosage regimens by Bayesian estimation methods.

Chromatography, High Pressure Liquid↗
PubMed1989

Pharmacokinetic modeling of ethyl loflazepate (Victan) and its main active metabolites.

A simultaneous consideration of plasma and urine data of unchanged drug and active metabolites, taking into account the metabolic process of the precursor, is described. The maximum likelihood principle was used to estimate parameters. This methodology is highly efficient in determining the contribution of the two main and active metabolites in the pharmacological response of ethyl loflazepate. It also may serve in the search for optimum dosage regimens in clinical practice.

Administration, Oral↗
PubMed1989

A limited sampling procedure for estimating adriamycin pharmacokinetics in cancer patients.

The aim of this study was to find a procedure allowing estimation of individual pharmacokinetic parameters for adriamycin with minimal cost and disturbance for the patient. Twenty-five patients with breast cancer were treated by short infusion of adriamycin at a dose of 12 mg m-2 week-1 (41 courses). Population characteristics were determined on 15 randomly chosen courses (10 patients, group I) in order to define two optimal sampling times (26 min and 24 h) and to perform Bayesian estimation on the remaining 26 courses (17 patients, group II). For patients of group II, Bayesian estimation (BE) associated with a reduced sub-optimal sampling protocol (20 min and 24 h) was compared with maximum likelihood estimation (MLE), the classical procedure. Regression analysis of clearance values obtained after BE versus MLE indicated a high correlation coefficient (r = 0.969) with the slope (a = 0.991 +/- 0.085) and the intercept (b = 2.271 +/- 4.810) close to 1 and 0 respectively. This original method is thus valid to measure accurately adriamycin clearance; it improves patient comfort and can be used routinely.

Adult↗
PubMed1989

Effect of renal failure on the pharmacokinetics of ethyl loflazepate (Victan) in man.

The kinetics of ethyl loflazepate were studied in patients with various degrees of renal failure. A strong correlation was noted between urinary excretion of metabolite loflazepate and creatinine clearance. In contrast, elimination half-life and total plasma clearance of the sum of loflazepate + descarboxyloflazepate seemed to be independent of the degree of renal impairment. These results indicate the absence of a risk of accumulation of the 2 main and active metabolites of ethyl loflazepate in patients with renal failure.

Administration, Oral↗
PubMed1988

The frozen hip.

Explore the source record for details and available documents.

Diagnosis, Differential↗
PubMed1988

Dynamical dosage regimen calculations in linear pharmacokinetics.

The objective of this analysis of a linear compartment system is to compute drug input functions that are optimal in producing nontoxic pharmacological responses of maximal therapeutic efficacy. Pharmacokinetics should underlie the rational use of drugs and when a therapeutic range is known, the achievement of safe and effective target concentrations may be assured by a dosage regimen computed for a given administration schedule. The method developed herein is based on linearity and superimposition principles applicable to the class of systems considered. This method requires estimated values of model individual parameters and computes optimum dosage regimens in an iterative scheme, corresponding to a real time dynamical context. An interactive computer program has been developed to perform dosage regimen calculations.

Amikacin↗
PubMed1988

Naproxen kinetics in synovial fluid of patients with osteoarthritis.

1. The kinetics of naproxen in synovial fluid were studied in 407 osteoarthritic outpatients with knee effusion requiring aspiration, following a single 1100 mg oral dose of naproxen sodium. 2. The drug concentration-time profiles were described by a biexponential function. Naproxen entered synovial fluid rapidly, reaching a maximum concentration of 36 mg l-1 (Cmax) at 7.5 h. The first order input rate constant (kOs) was 0.41 +/- 0.15 h-1 with a lag time (tlag) of 0.24 +/- 0.36 h. 3. Elimination from the fluid was slow (t1/2 = 31 +/- 12 h) and appreciable drug concentrations were still measurable (27 mg l-1) after 24 h. 4. During once daily dosing of naproxen sodium, naproxen should accumulate in synovial fluid, a steady-state being achieved within a week of treatment. The predicted accumulation ratio based on trough concentration was 2.4.

Adult↗
PubMed1988

New approach in bioavailability study of two formulations of ethyl loflazepate.

The disposition of ethyl loflazepate (Victan) was studied on 12 healthy male volunteers after administration of the two oral formulations of the drug: one 4-mg tablet and two 2-mg tablets according to an open crossover single dose comparison. A model-independent analysis and a model-dependent approach were used to treat experimental data. Appropriate statistical tests (ANOVA, Wilcoxon test, Westlake test for model-independent parameters; principal components analysis, Hotelling T2 test for model-dependent parameters) demonstrated the bioequivalence of the two formulations.

Administration, Oral↗
PubMed1988

[Pharmacokinetics in phase IV studies for the preview of a therapeutic protocol].

The pharmacokinetic studies of anticancer drugs still go on after they are out on the market. The therapeutic protocol is then more precise and depends on the dosage results of these drugs. Some examples of dosage adjustment according to their plasmatic level are reported here for high-dose methotrexate infusion and for CDDP infusion over five days. The test dose and the bayesian method (pharmacokinetic population) are used to predict the adapted individualized dosage for each patient.

Antineoplastic Agents↗
PubMed1987

Clinical pharmacokinetics of the antitumor drug navelbine (5'-noranhydrovinblastine).

Eleven patients with advanced cancer received navelbine (15 mg/m2) as a single i.v. bolus injection. At least 1 week later, the patients were given a 2-fold increased dose of navelbine (30 mg/m2) and, for seven of them, the 30-mg/m2 dose was repeated after a delay longer than a week. After each administration, plasma and urine were collected for 72 h and monitored for navelbine concentration by radioimmunoassay. The comparison of dose-normalized plasma level profiles showed significant time dependence (P less than 0.05) in four of the seven assessable patients. Some patients also exhibited significant (P less than 0.05) nonlinear (dose dependent) kinetic profiles. Only 3 of the 10 appreciable patients were characterized by both time independent and linear profiles. However, the plasma concentration decay curves presented a triphasic shape similar to that obtained with other antitumor Vinca alkaloids and the data were consistent with a three-compartment pharmacokinetic model. The dose and/or time dependence evidenced for most of the patients did not result in marked changes in pharmacokinetic parameters among courses. The pharmacokinetics of navelbine were characterized by a high plasma clearance (0.27 to 1.49 liter.h-1.kg-1), a large distribution volume (8.2 to 48.2 liter.kg-1), and a long terminal half-life (22.1 to 67.8 h). Urine excretion was low (less than 7.9%). Thus, navelbine pharmacokinetics resembles that of other antitumor Vinca alkaloids.

Adult↗
PubMed1987

Pharmacokinetics of methotrexate and 7-hydroxy-methotrexate after methotrexate infusions.

Methotrexate was administered by IV infusion, 2g (1.19 +/- 0.05 g/m2) over 24 hours, to a homogeneous group of patients undergoing treatment for breast cancer. Three courses were given at three week intervals. Methotrexate and 7-hydroxy-methotrexate plasma and urine pharmacokinetics were investigated. The average terminal half-lives of methotrexate and 7-hydroxy-methotrexate in plasma were 15.02 and 15.19 hours respectively. The area under concentration-time curve was 723.8 +/- 196.4 microM x h for methotrexate and 598.1 +/- 212.5 microM x h for 7-hydroxy-methotrexate. The total average urinary excretions of methotrexate and 7-hydroxy-methotrexate over a 96 hour period were 52% and 5.4% respectively. Urinary clearance of methotrexate was 3.46 +/- 1.4 1/h. In contrast, urinary excretion of 7-hydroxy-methotrexate was not linear. These results confirm the protein binding of metabolite to serum albumin and may suggest that distribution of 7-hydroxy-methotrexate is different from unchanged drug or that the metabolite can be eliminated by another route, such as bile.

Aged↗
PubMed1986

Pharmacokinetics of isosorbide dinitrate and its mononitrate metabolites after intravenous infusion.

Plasma concentrations of isosorbide dinitrate (ISDN) and its two active metabolites 2-isosorbide mononitrate (2-ISMN) and 5-isosorbide mononitrate (5-ISMN) have been measured during and for 6 hr after intravenous infusion at a rate of 2.5 mg/hr during 1.75 hr in six cardiac patients, by a capillary gas chromatographic method. Data were analyzed by simultaneous modeling of the observed kinetics of the three compounds. Two or three phases were detected on the postinfusion ISDN concentration-time curves. ISDN concentrations declined with a mean terminal half-life of 2.81 hr +/- 0.7 SD. The mean systemic clearance of ISDN (2.9 L/min +/- 0.7 SD) and its mean total volume of distribution (259 L +/- 48 SD) were relatively high. Plasma 5-ISMN concentrations were 5- to 6-fold greater than those of 2-ISMN during the whole observation period. Maximum levels of 2-ISMN (6.7 ng/ml +/- 0.9 SD) and of 5-ISMN (27 ng/ml +/- 6 SD) occurred within a few minutes after the end of infusion. The mean half-lives of 2-ISMN (1.59 hr +/- 0.19 SD) and of 5-ISMN (3.78 hr +/- 0.79 SD) estimated by the model were smaller than those calculated by a model-independent method (2.95 hr +/- 0.41 SD and 5.98 hr +/- 2.22, respectively), but were in good agreement with those reported in the literature following separate administration of both metabolites to man. This study shows how such modeling can distinguish between metabolite formation and elimination processes and allow the determination of metabolite half-lives after administration of the precursor drug.

Adult↗
PubMed1986

Steady-state dosage regimen calculations in linear pharmacokinetics.

This paper describes a general approach to compute steady-state dosage regimens. The method deals with individual linear compartmental mammillary pharmacokinetic models and requires estimated values of model parameters. It is based on the linearity principle and computes dosage regimens to achieve and maintain specified steady-state plasma concentrations, e.g. mean value or minimum effective and maximum safe levels. An interactive computer program performing the calculations has been developed.

Administration, Oral↗
PubMed1985

Bayesian estimation and prediction of clearance in high-dose methotrexate infusions.

Much attention has been paid to the problem of estimating the pharmacokinetic parameters of individual patients in order to optimize dosage choices. Individual kinetics determined by test-dose bolus injection are a basis for predicting drug concentrations after high-dose methotrexate infusion and for computing appropriate dosages. Simplifications may be attempted, even allowing the test-dose to be omitted by using Bayesian estimation rather than likelihood estimation. To individualize pharmacokinetic parameters, Bayesian estimation combines information about population characteristics and those of individuals based on few measured plasma levels during high-dose infusion. Application of this procedure to methotrexate reveals interesting predictive performances and ability to handle variation due to intraindividual time variability without using test doses. The methodology promises to be more efficient in computing dosages in order to avoid toxic levels and will be less expensive in routine clinical use.

Aged↗
PubMed1985

Pharmacokinetics and metabolism of epirubicin during repetitive courses of administration in Hodgkin's patients.

We studied the pharmacokinetics and metabolism of epirubicin (4'-epidoxorubicin) in ten patients suffering from Hodgkin's disease and receiving three successive injections of epirubicin at 15-day intervals in a combined chemotherapy regimen. Doses were either constant (35 mg/m2) or escalated from 25 to 35 and 50 mg/m2. Epirubicin metabolism was characterized by the presence of high levels of epirubicin glucuronide in plasma and urine. The area under the time-concentration plasma curve of epirubicin glucuronide reached almost that of unchanged epirubicin (mean ratio = 0.7-0.85), whereas the cumulative urinary excretion of epirubicin glucuronide was one-half of that of epirubicin (mean ratio = 0.45-0.51). Repeating or escalating the doses did not change the levels of the glucuronide significantly. Only a trend towards higher relative levels of glucuronide could be noticed at the lowest dose. The pharmacokinetic parameters of epirubicin were characterized by a high total plasma clearance (mean value: 70-85 1/hr) and a mean elimination half-life of 25-35 hr. Repeating or escalating the doses was followed by a slight increase of the total plasma clearance in most patients, without changes of the elimination half-life. The cumulative urinary excretion was 11-12% of the dose administered and did not vary significantly as a function of time or dose.

Adult↗
PubMed1985

Dosage predictions in high-dose methotrexate infusions. Part 1: Evaluation of the classic test-dose protocol.

A preliminary methotrexate (MTX) kinetic evaluation following administration of an IV bolus (test-dose) allowed individualization of high-dose infusions (HD-MTX). This approach combined with therapeutic drug monitoring was found to have good performance over a large scale of predicted steady-state levels (Css) (10(-5) to 10(-4) M over 24 to 36 h) corresponding to 17 to 650 mg/h deliveries (root mean squared error : rmse (precision) = 1.54 X 10(-5) M (21.4%) and mean error : me (bias) = 0.043 X 10(-5) M (NS)). However a significative (p less than 0.05) but rather low over-estimation of dosage (me = 7.38 X 10(-5) M (14.8%)) associated to a decrease in the prediction precision (rmse = 13.3 X 10(-5) M (26.6%)) occurred in 5 X 10(-4) M predicted Css over 8 h (970 to 1970 mg/h deliveries). However in a number of cases (6 out of 29) important deviations from predicted Css occurred, implying the need to stop the infusion before 8 h. These results indicated that MTX pharmacokinetics was linear from low test-dose bolus injections to high-dose infusions. This allowed dosage predictions based upon preliminary estimation of MTX clearance and associated to therapeutic drug monitoring during and following infusion.

Head and Neck Neoplasms↗