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A Iliadis

Publications and source records attributed to A Iliadis.

67 records · Page 4Linked to original sources
PubMed1985

Dosage predictions in high-dose methotrexate infusions. Part 2: Bayesian estimation of methotrexate clearance.

Population pharmacokinetics of methotrexate (MTX) was evaluated from intravenous test-dose (TD) data (n = 20 corresponding to 174 measured samples). Bayesian prediction of MTX clearance from TD experiments combining population data with measured levels (at times 0.5 and 6 h) was found to be feasible in routine situations with good performance (root mean squared error : rmse (precision) = 1.14 1.h-1 (11.2%) and mean error : me (bias) = 0.06 1.h-1 (NS) relatively to weighted least-square estimates, n = 50). The precision of Bayesian prediction was comparable to that of the model independent which is used in routine practice and involves 9 measured levels over 30 h, (rmse = 1.35 1.h-1 (10.9%), n = 50). However, the routine method presented a significative bias (me = -0.81 1.h-1, n = 50).

Humans↗
PubMed1985

Comparative pharmacokinetics and metabolism of doxorubicin and epirubicin in patients with metastatic breast cancer.

We have studied the metabolism and pharmacokinetics of epirubicin (4'-epidoxorubicin), as compared to those of doxorubicin, in a total of 16 patients with metastatic breast cancer. Epirubicin metabolism markedly differs from that of doxorubicin, in that large amounts of glucuronides of epirubicinol and epirubicin were observed in plasma as well as in urine samples. The total plasma clearance of epirubicin was significantly higher than that of doxorubicin; this was interpreted as due to an increase of the distribution volume of epirubicin, since the terminal plasma half-lives of both drugs were similar. No significant modifications were observed in patients with hepatic metastases. The differences in the pharmacokinetic and metabolic properties of the two drugs may be responsible for the differences in toxicity that have been noticed between them in previous phase I and II studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Assay of methotrexate and 7-hydroxymethotrexate by gradient-elution high-performance liquid chromatography and its application in a high-dose pharmacokinetic study.

A paired-ion high-performance liquid chromatographic method is described for the simultaneous determination of methotrexate (MTX) and its major metabolise, 7-hydroxymethotrexate (7-OH-MTX), in plasma and urine. In addition, this technique permits the separation of other known metabolites of MTX, such as DAMPA and MTX-polyglutamates. After selective extraction on an anion-exchange resin column, both compounds and the internal standard, aminopterin, were separated on a reversed-phase octadecylsilane column with UV-detection at 313 nm. The detection limits for plasma and urine samples were approximately 40 ng/ml (8.8 x 10(-8) M) for MTX and 100 ng/ml (2.1 x 10(-7) M) for 7-OH-MTX. This method was applied in pharmacokinetic studies following 24-h infusion of high-dose MTX in four patients during two successive treatments. After the end of the infusion, the mean apparent half-life for the metabolite was 19.1 h, while that for MTX was 8.8 h. A stepwise increase in the plasma concentrations of both MTX and its metabolite was observed during the second MTX infusion. This increase was reflected in the cumulative urinary excretion of both drug and its metabolite.

Journal Article↗
PubMed1983

Time dependency of adriamycin and adriamycinol kinetics.

Adriamycin was administered by IV injection to seven patients with various solid tumors at a dose of 30 mg/m2 during successive courses. Extraction was carried out by the SEP-PAK method for plasma and by solvents for urine. Plasma and urinary levels of adriamycin and adriamycinol were determined by high-performance liquid chromatography over 72-h period after injection. Pharmacokinetic parameters for adriamycin and adriamycinol were calculated for each course of treatment. The results show significant inter- and intra-individual variations in the kinetics and elimination of both compounds. The analysis of pharmacokinetic data reveals a wide variability in the fluctuations observed during the successive courses in different patients. This study confirms the time-dependency of ADR kinetics.

Adult↗
PubMed1983

[Pharmacokinetic study of doxorubicin in the treatment of malignant non-Hodgkin's lymphomas].

We have studied the plasma kinetics of doxorubicin treatment in nine patients with non-Hodgkin's malignant lymphoma. Four patients were studied following the first two injections of this drug, the other five patients were studied only after the first injection. Our results corroborate the existence of three successive phases of doxorubicin plasma decay, with mean half-lives of 3.81 min, 1.19 h and 29 h. We observed an important variation of the pharmacokinetic parameters related to the distribution volumes. The total plasmatic clearance ranged between 32 and 67 l/h. The kinetics of doxurubicin are time-dependent, i.e. an important variation of the pharmacokinetic parameters related to the distribution volumes. The total plasmatic clearance ranged between 32 and 67 l/h. The kinetics of doxurubicin are time-dependent, i.e. an important variation of the pharmacokinetic parameters existed after the 2nd injection of the drug in three out of four patients. These 3 patients showed either an increase of the elimination half-life (1 case) or an increase of the distribution volume (1 case) or a decrease of the distribution volume (1 case) after the 2nd injection. We observed a significant correlation between the age of the patients and the early clearance of the drug, the youngest patients eliminating the drug more rapidly than the oldest ones. This observation may lead to the administration of different dosages of doxorubicin according to the age of the patient.

Adolescent↗
PubMed1983

Pharmacokinetic study of ethanol after oral administration: a new approach to enzymatic elimination.

A new approach to the enzymatic elimination of ethanol in vivo allows us by means of a one-compartment model to take into account all the phases of the ethanol concentration-time curve after oral administration. The Michaelis-Menten equation is an approximation of this model; indeed it constituted the only non-linear approach to the kinetic study of ethanol. To express the model in the form of an equation leads to a third-order system of bilinear differential equations which has no analytical solution. The identification of the model is based on the optimization of a conformity criterion between experimental values and those predicted by the model. Optimization is performed by means of an iterative algorithm minimizing non-linear functions. This method permits the estimation of initial concentrations of products involved in the enzymatic reaction (substrate, enzyme) and kinetic constants (characterizing absorption and enzymatic reaction). Kinetics in nonalcoholics, alcoholics, and former alcoholics were identified using this new model. A good fit between the experimental values and the simulated curve was obtained. The in vivo estimation of the kinetic constants of each elementary step of the enzymatic reaction represents an original approach likely to provide more knowledge of ethanol metabolism.

Adult↗
PubMed1982

[Approach to ethanol metabolism in man by studying the concentration-time curves of ethanol, free enzyme and plasma acetate (author's transl)].

The use of a pharmacokinetic model characterized by a new theoretical approach of the enzymatic reaction allows to account for ethanol concentration-time curve (after oral administration in man) and to simulate the evolution of free enzyme concentration. The interpretation of the various phases observed during these kinetics (ethanol, free enzyme) and plasma acetate kinetics (performed in the same study) constitutes an original approach to ethanol metabolism.

Acetates↗
PubMedDate not supplied

Multiple-dose pharmacokinetics of the new H1-receptor antagonist tazifylline in healthy volunteers.

The multiple-dose pharmacokinetics of the new H1-receptor antagonist, tazifylline, were investigated in healthy volunteers. From single-dose data, tazifylline appeared to be rapidly absorbed (median tmax of 0.6 h) and eliminated (t1/2 = 1.0 +/- 0.2 h). However, plasma levels measured on days 3 and 8 of the multiple-dose regimen (10 mg b.i.d. for 8 days) indicated moderate accumulation. A two-compartment model best described multiple-dose data with a terminal half-life of 15.6 +/- 7.6 h consistent with twice-daily dosing of tazifylline.

Adult↗
PubMedDate not supplied

Non-linear kinetics of ethanol elimination in man: medico-legal applications of the terminal concentration-time data analysis.

Research regarding parameters suitable for reporting on the activity of enzymatic systems responsible for ethanol metabolism is of obvious interest in medico-legal practice. Blood ethanol concentration-time curves, following oral administration of ethanol, have been developed for ethylic and non-ethylic subjects. This study has confirmed the non-linear kinetics of ethanol elimination; however, existing non-linear models appear to be inadequate for usual medico-legal practice, because of their complexity. We observed three phases during the elimination of ethanol. The first order terminal phase is characterized by its half-life. This parameter seems adequate as a basis for determining the activity of enzyme systems responsible for the metabolism of ethanol.

Adult↗
PubMedDate not supplied

Evolution of plasma acetate concentration during ethanol metabolism in man.

Following oral administration of ethanol to ethylic as well as non-ethylic volunteers, the entire time course of plasma acetate concentration has been observed. The curve shows a typical evolution in three phases: (1) a quick ascending phase (2) a steady state characterized by a mean concentration (-C) (3) a first-order decrease, characterized by its half-life (t1/2) These parameters show significant variations (increase of -C, decrease of t1/2) in the ethylic subjects, in comparison with the non-ethylic ones. The variation of the area under the acetate curve according to the dose of ethanol given, is linear. The comparison of such a development with the one, typically non-linear, of the area under ethanol curve previously analyzed for the same subjects, may guess the origin of the non-linearity of ethanol kinetics.

Acetates↗
PubMedDate not supplied

Ursodeoxycholic acid modulates cyclosporin A oral absorption in liver transplant recipients.

The aim was to study the ursodeoxycholic acid (UDC) effect on the cyclosporin A (CsA) pharmacokinetics after oral administration of the microemulsion formulation Neoral (CsA-ME) in liver transplant recipients, and test the potential protective effect of this bile acid on liver and renal CsA-ME-induced toxicity. At entry into the study, 12 patients who underwent orthotopic liver transplantation received CsA-ME, for at least 6 months. They then received a cotreatment CsA-ME plus UDC (13.8 mg x kg(-1) x day(-1)) for three months. Blood concentrations of CsA were measured using a monoclonal antibody specific for the parent compound. The kinetic data were analysed by a mathematical model incorporating a time dependent rate coefficient for CsA intestinal absorption, before and after UDC treatment. Changes in serum markers of hepatic and renal injury were assessed. Individual serum bile acids were determined by chromatography. Serum levels of UDC increased from 3 to about 45% of total serum bile acids after UDC treatment. The estimated model parameters indicate that UDC administration modulates CsA intestinal absorption. In the nine non-cholestatic patients, UDC reduced the absorption rate and the bioavailability of CsA without modifying the elimination rate constant of CsA and the CsA pre-drug levels. In contrast, in the three cholestatic patients, the bioavailability tended to be higher and the absorption rate faster when CsA was combined with UDC. UDC significantly decreased elevated gamma-glutamyl transferase and creatinine serum levels and induced some clinical improvements such as disappearance of headaches in four patients. In conclusion, a 3-month UDC treatment modifies CsA intestinal absorption without affecting CsA elimination rate constant. On the other hand, UDC supplementation appears to improve CsA tolerability.

Absorption↗