当前位置： SCI文献检索 > EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS期刊下所有文献 > Multiplicative dependence of the first order rate constant and its impact on clinical pharmacokinetics and bioequivalence.

Multiplicative dependence of the first order rate constant and its impact on clinical pharmacokinetics and bioequivalence.

Abstract：

:The purpose of the study was to investigate the factors upon which the first order rate constant depends in order to assess the impact on the body-drug concentration when it changes throughout a treatment. A reasoning for linking the first order rate constants with several factors in a multiplicative way was proposed out taking into account kinetic and thermodynamic aspects. A multi-compartment model for drug disposition was analyzed and compartment mean drug concentrations at steady state were obtained as a function of the model kinetic constants. At the moment, only four factors were identified as responsible for the actual rate constant value. Apart from an intrinsic kinetic constant, they are the inverse of compartment volume, the transfer surface area, the fraction of mass able to be transferred, and the fraction of mass that effectively can be transferred. In clinical practice some of these factors might change throughout time (because of chronophysiological rhythms or drug availability at the action sites) and consequently, an inconstant extra-plasma/plasma drug concentration ratio could be obtained. In conclusion, therapeutic response prediction for a treatment does not upon plasma drug concentration monitoring. Equivalence in plasma drug exposure should not mean therapeutic equivalence, because differences in the rate and in the extent between test and reference products may induce a change in the action site/plasma drug concentration ratio.

journal_name

Eur J Drug Metab Pharmacokinet

journal_title

European journal of drug metabolism and pharmacokinetics

authors

Fagiolino P

doi

10.1007/BF03190573

keywords:

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

43-9

issue

1

eissn

0378-7966

issn

2107-0180

journal_volume

29

pub_type

杂志文章

相关文献

EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS文献大全
  • The metabolism and excretion of 7-mono-0-(beta-hydroxyethyl) rutoside in the dog.

    abstract：:Following i.v. administration of mono-HR to the beagle, plasma levels of both mono-HR and its glucuronide conjugates fell rapidly, neither being detectable 8 h after injection. Following oral administration of 14C-mono-HR, mono-HR-glucuronide was detected in plasma, confirming the absorption of mono-HR, and low levels...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189428

    authors： Hackett AM,Griffiths LA

    更新日期：1979-01-01 00:00:00

  • Ocular distribution of cyclosporin A (Sandimmun) following systemic and topical administration to rabbits.

    abstract：:The purpose of this study was to determine the distribution of cyclosporin A (CsA) in various ocular fluids and tissues in the rabbit by two routes of administration. CsA was administered to two groups of two rabbits either by intramuscular route at a dose of 25 mg/kg/day or by local route using eyedrops, at a dose of...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：

    authors： Vernillet L,Lundh RL,Acezat-Mispelter F,Goizel C,Humbert H,Pouliquen Y

    更新日期：1991-01-01 00:00:00

  • Pharmacokinetics of natural borneol after oral administration in mice brain and its effect on excitation ratio.

    abstract：:Previous studies have indicated that borneol has double side effects on the central nervous system (CNS), but the mechanism is unknown. The aim of this study was to clarify the relationship between excitation ratio [contents of excitatory amino acids (AAs) versus that of inhibitory] and the content of natural borneol ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-011-0058-5

    authors： Li WR,Chen RY,Yang L,Huang TL,Xu QW,Mi SQ,Wang NS

    更新日期：2012-03-01 00:00:00

  • Pharmacokinetic study of doxycycline polyphosphate (PPD), hydrochloride (CHD) and base (DB).

    abstract：:Six healthy volunteers received the same oral dose of doxycycline, base (200 mg). Each received two of the three preparations at two-week intervals. Experimental results were interpreted on the basis of one or two-compartment models. The three preparations gave the elimination constants of the same order of magnitude ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189510

    authors： Saux MC,Mosser J,Pontagnier H,Leng B

    更新日期：1981-01-01 00:00:00

  • Pharmacokinetic evaluation of guar gum-based colon-targeted oral drug delivery systems of metronidazole in healthy volunteers.

    abstract：:The present study was carried out to find the in vivo performance of guar gum-based colon-targeted tablets of metronidazole as compared to an immediate release tablets in human volunteers. Six healthy volunteers participated in the study and a crossover design was used. Blood samples were obtained at different time in...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF03220181

    authors： Krishnaiah YS,Veer Raju P,Dinesh Kumar B,Jayaram B,Rama B,Raju V,Bhaskar P

    更新日期：2003-10-01 00:00:00

  • Effect of metal salts on UDPglucuronosyltransferase activity of various aglycones in rat liver microsomes in vitro.

    abstract：:The effects of aluminium, manganese, ferrous and ferric iron, cobalt, nickel, copper, zinc, cadmium, barium, mercury and lead ions on the rat hepatic UDPglucuronosyltransferase activity with regard to 4-methylumbelliferone, 4-nitrophenol, bilirubin, and 2-aminophenol were investigated in vitro. Conjugation of bilirubi...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189441

    authors： Aitio A,Ahotupa M,Parkki MG

    更新日期：1980-01-01 00:00:00

  • Identification of Transporters Involved in Beraprost Sodium Transport In Vitro.

    abstract：BACKGROUND AND OBJECTIVE:Beraprost sodium (BPS) is a chemically stable and orally active prostacyclin analog that is used in the treatment of chronic arterial occlusive disease since 1992 and primary pulmonary hypertension since 1999 in Japan. Multiple-drug therapy is common in clinical practice, and BPS is co-administ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-016-0327-4

    authors： Oshida K,Shimamura M,Seya K,Ando A,Miyamoto Y

    更新日期：2017-02-01 00:00:00

  • Induction and inactivation of a cytochrome P450 confering herbicide resistance in wheat seedlings.

    abstract：:Cytochrome P450-dependent enzymes from wheat catalyze the oxidation of endogenous compounds (lauric and oleic acids) and of several herbicides (diclofop, chlortoluron, bentazon). Treatment of wheat seedlings with the safener, naphthalic anhydride and with phenobarbital increases dramatically several P450-dependent enz...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190370

    authors： Forthoffer N,Helvig C,Dillon N,Benveniste I,Zimmerlin A,Tardif F,Salaün JP

    更新日期：2001-01-01 00:00:00

  • Clinical Pharmacokinetics of a Lipid-Based Formulation of Risperidone, VAL401: Analysis of a Single Dose in an Open-Label Trial of Late-Stage Cancer Patients.

    abstract：BACKGROUND AND OBJECTIVES:A clinical trial was conducted to measure and analyse the pharmacokinetic parameters of a lipid formulation of risperidone, VAL401. The VAL401 formulation is designed to repurpose risperidone from an antipsychotic to an adenocarcinoma treatment, with the lipid formulation altering the cellular...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-018-00538-4

    authors： Dilly SJ,Morris GS,Taylor PC,Parmentier F,Williams C,Afshar M

    更新日期：2019-08-01 00:00:00

  • Altered Expression of Transporters, its Potential Mechanisms and Influences in the Liver of Rodent Models Associated with Diabetes Mellitus and Obesity.

    abstract：:Diabetes mellitus is becoming an increasingly prevalent disease that concerns patients and healthcare professionals worldwide. Among many anti-diabetic agents in clinical uses, numerous reports are available on their altered pharmacokinetics because of changes in the expression of drug transporters and metabolic enzym...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章,评审

    doi：10.1007/s13318-015-0306-1

    authors： Ma L,He L,Wang L,Li L,Lin X,Pan G

    更新日期：2016-06-01 00:00:00

  • Absolute bioavailability study in the dog with Visacor, a new cardioselective beta blocking drug with intrinsic sympathomimetic activity.

    abstract：:The cardioselective beta-adrenergic blocking drug Visacor (ICI 141,292) was dosed to six beagle dogs in a randomized cross-over manner. Five formulations were examined i.e. a 15 mg/kg intravenous solution, a 50 mg/kg oral solution, and 50, 100 and 200 mg/kg oral powder formulations. Whole blood and urine samples were ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03189616

    authors： McAinsh J,Smith RP,Ferguson RA

    更新日期：1984-04-01 00:00:00

  • Parameterization of Microsomal and Cytosolic Scaling Factors: Methodological and Biological Considerations for Scalar Derivation and Validation.

    abstract：:Mathematical models that can predict the kinetics of compounds have been increasingly adopted for drug development and risk assessment. Data for these models may be generated from in vitro experimental systems containing enzymes contributing to metabolic clearance, such as subcellular tissue fractions including micros...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-020-00666-w

    authors： Doerksen MJ,Jones RS,Coughtrie MWH,Collier AC

    更新日期：2020-12-19 00:00:00

  • Prediction of the Oral Bioavailability Correlation Between Humans and Preclinical Animals.

    abstract：BACKGROUND:Experimental determination of a drug's oral bioavailability in humans is cost and time consuming; therefore, is usually performed on preclinical animals. It is believed that animal data are predictive of human data; however, there are some doubts regarding the reliability of this concept. The aim of this stu...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-020-00636-2

    authors： Beheshti S,Shayanfar A

    更新日期：2020-12-01 00:00:00

  • Metabolism of the new alpha-1A-adrenergic receptor antagonist, phthalimide-phenylpiperazine analog (RWJ-69442), in rat, dog and human hepatic S9 fractions, and in rats.

    abstract：:The in vitro and in vivo metabolism of RWJ-69442, an alpha-1A-adrenergic receptor antagonist, was investigated after incubation with rat, dog, and human hepatic S9 fractions in the presence of NADPH-generating system, and a single oral/iv dose administration to rats (oral: 100 mg/kg; iv: 10 mg/kg). Unchanged RWJ-69442...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03226416

    authors： Wu WN,McKown LA,Kuo GH

    更新日期：2005-01-01 00:00:00

  • Effect of induced hypoalbuminemia on distribution, total clearance and unbound clearance of piroxicam in vivo in the rat.

    abstract：:The influence of decreased albumin concentration on the pharmacokinetic behaviour of Piroxicam was studied in vivo in rats that had undergone plasmapheresis. Reductions of approximately 25% and 50% in the plasma albumin concentration were achieved, the former in rats not given plasma expander, the latter in animals gi...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03188792

    authors： Troconiz JI,Lopez-Bustamante LG,Fos D

    更新日期：1993-04-01 00:00:00

  • The Effects of CYP3A5 Genetic Polymorphisms on Serum Tacrolimus Dose-Adjusted Concentrations and Long-Term Prognosis in Chinese Heart Transplantation Recipients.

    abstract：BACKGROUND AND OBJECTIVES:Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-019-00563-x

    authors： Liu BY,Chen WQ,Chen ZG,Huang J,Liao ZK,Liu Q,Zheng Z,Song YH,Wang W,Hu SS

    更新日期：2019-12-01 00:00:00

  • Functional characterization of cynomolgus monkey UDP-glucuronosyltransferase 1A9.

    abstract：:UDP-glucuronosyltransferase 1A9 (UGT1A9) contributes to the glucuronidation of numerous drugs. Cynomolgus monkeys are regarded as experimental animals similar to humans in studies on safety evaluation and biotransformation for drug development. In this study, the similarities and differences in the enzymatic propertie...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-014-0177-x

    authors： Yamamoto K,Mukai M,Nagaoka K,Hayashi K,Hichiya H,Okada K,Murata M,Shigeyama M,Narimatsu S,Hanioka N

    更新日期：2014-09-01 00:00:00

  • Pharmacokinetic studies on IdB 1016, a silybin- phosphatidylcholine complex, in healthy human subjects.

    abstract：:IdB 1016 is a complex of silybin (the main active component of silymarin) and phosphatidylcholine, which in animal models shows greater oral bioavailability and therefore greater pharmacological activity compared with pure silybin and silymarin. In order to assess its pharmacokinetic profile in man, plasma silybin lev...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章,随机对照试验

    doi：10.1007/BF03190223

    authors： Barzaghi N,Crema F,Gatti G,Pifferi G,Perucca E

    更新日期：1990-10-01 00:00:00

  • The role of drug lipophilicity in release from intra-adipose and intramuscular injection sites.

    abstract：:Release rates from intramuscular and intra-adipose injection sites are dependent upon several including injection depth. Little is known about the relationship between drug lipophilicity and transport rate of drugs through adipose and muscle tissue. The principal objective of the present study was to investigate to wh...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：

    authors： Kadir F,Zuidema J,Pijpers A,Vulto A,Verheijden JH

    更新日期：1991-01-01 00:00:00

  • Pharmacokinetics of recombinant human basic fibroblast growth factor in mice using a radioiodination method combined with SDS-PAGE and a sandwich enzyme-linked immunosorbent assay.

    abstract：:Pharmacokinetics of recombinant human basic fibroblast growth factor (rhbFGF) in mice were studied by using a radioiodination method combined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and a sandwich enzyme-Linked immunosorbent assay (ELISA). RhbFGF concentration in serum were dertermine...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190593

    authors： Zhang Q,Wang GJ,Sun JG

    更新日期：2004-07-01 00:00:00

  • Study of the disposition kinetics of the N-oxide-derivative: a metabolite of picobenzide.

    abstract：:The disposition kinetics of the N-oxide of picobenzide were studied after administration to rabbits at a bolus dose of 30 mg/kg of picobenzide intravenously. The biotransformation process fits a first-order kinetic process, and the metabolite shows good access capacity to the peripheral compartment. The N-oxide of pic...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190837

    authors： Santos Buelga D,Mariño EL,Domínguez-Gil A

    更新日期：1989-01-01 00:00:00

  • Bioequivalence studies: biometrical concepts of alternative designs and pooled analysis.

    abstract：:A bioequivalence study compares the bioavailability between a test and a reference drug product in terms of the rate and extent of drug absorption. Area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) are the pharmacokinetic parameters that serve as characteristics for the asses...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190024

    authors： Zintzaras E,Bouka P

    更新日期：1999-07-01 00:00:00

  • Use of bile correction factors for allometric prediction of human pharmacokinetic parameters of torcetrapib, a facile cholesteryl ester transfer protein inhibitor.

    abstract：:Torcetrapib was the lead candidate belonging to the class of cholesteryl ester transfer protein (CETP) inhibitor which was being developed for the management of cardiovascular risk factors by raising HDL. The availability of pharmacokinetic parameters (clearance: CL/F, volume of distribution: Vd/F, elimination rate co...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03191385

    authors： Mullangi R,Ahlawat P,Trivedi RK,Srinivas NR

    更新日期：2009-01-01 00:00:00

  • Chemical substance kinetics in the case of chronobiological variations of elimination rate.

    abstract：:This study describes an approach permitting the determination of compartmental concentration and drug kinetics in the case of chronobiological variations of elimination rate. ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03190035

    authors： Merabet-Atmani G,Aliguechi-Bouhadja S,Redouane A,Filali T,Mansour K

    更新日期：1999-10-01 00:00:00

  • Pharmacokinetic and pharmacodynamic aspects of concomitant mibefradil-digoxin therapy at therapeutic doses.

    abstract：:This study investigated the effect of mibefradil on digoxin pharmacokinetics an pharmacodynamics. Following a loading dose of digoxin (0.375 mg, three times, day 1), 0.375 mg was administered once daily to 40 healthy subjects (days 2-15). Mibefradil was administered daily at 50 mg, 100 mg, or 150 mg (days 9-15). With ...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF03190358

    authors： Peters J,Welker HA,Bullingham R

    更新日期：1999-04-01 00:00:00

  • First pass effect of pinazepam in the rabbit liver.

    abstract：:The liver first pass effect of pinazepam in four anaesthetized rabbits was determined by measuring the concentrations of this compound and those of its metabolite N-desmethyldiazepam in the plasma from the portal and hepatic veins. Anaesthesia was induced with an i.p. injection of urethane (1.5 g/kg). Portal and hepat...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/BF03188728

    authors： Pacifici GM,Placidi GF

    更新日期：1982-01-01 00:00:00

  • Effects of acylcarnitines on efflux transporting system in Caco-2 cell monolayers.

    abstract：:This study examined the effects of the absorption enhancers, acylcarnitines, on efflux transporting systems, including P-glycoprotein (P-gp) and other efflux transporters, and elucidated the importance of acyl chain length and the concentration of acylcarnitine on the activity of efflux transport. The effects of two a...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-010-0001-1

    authors： Tomita M,Doi N,Hayashi M

    更新日期：2010-09-01 00:00:00

  • Influence of hepatic impairment on the pharmacokinetics of the dopamine agonist rotigotine.

    abstract：:The transdermally applied dopamine receptor agonist rotigotine is extensively metabolized in the liver. An open-label, parallel-group study was conducted to evaluate the effects of moderate hepatic impairment on the pharmacokinetics, safety and tolerability of rotigotine. Eight subjects with normal hepatic function an...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s13318-013-0153-x

    authors： Cawello W,Fichtner A,Boekens H,Braun M

    更新日期：2014-09-01 00:00:00

  • Population Pharmacokinetic Analyses of Lithium: A Systematic Review.

    abstract：BACKGROUND AND OBJECTIVES:Even though lithium has been used for the treatment of bipolar disorder for several decades, its toxicities are still being reported. The major limitation in the use of lithium is its narrow therapeutic window. Several methods have been proposed to predict lithium doses essential to attain the...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章,评审

    doi：10.1007/s13318-017-0421-2

    authors： Methaneethorn J

    更新日期：2018-02-01 00:00:00

  • Method of variability optimization in pharmacokinetic data analysis.

    abstract：:For many drugs administered per os, high variability in the concentration-time (C-T) values from first sampling to the phase of distribution may cause difficulty in pharmacokinetic analysis. Therefore, the aim of this study was to propose a method of transformation of C-T data, which would allow significantly reducing...

    journal_title：European journal of drug metabolism and pharmacokinetics

    pub_type： 杂志文章

    doi：10.1007/s13318-013-0145-x

    authors： Grabowski T,Jaroszewski JJ,Piotrowski W,Sasinowska-Motyl M

    更新日期：2014-06-01 00:00:00