Effect of diabetes mellitus on pharmacokinetic and pharmacodynamic properties of drugs.

Abstract:

:The effects of diabetes mellitus on the pharmacokinetics and pharmacodynamics of drugs have been well described in experimental animal models; however, only minimal data exist for humans and the current knowledge regarding the effects of diabetes on these properties remains unclear. Nevertheless, it has been observed that the pharmacokinetics and pharmacodynamics of drugs are changed in subjects with diabetes. It has been reported that diabetes may affect the pharmacokinetics of various drugs by affecting (i) absorption, due to changes in subcutaneous adipose blood flow, muscle blood flow and gastric emptying; (ii) distribution, due to non-enzymatic glycation of albumin; (iii) biotransformation, due to regulation of enzymes/transporters involved in drug biotransformation; and (iv) excretion, due to nephropathy. Previously published data also suggest that diabetes-mediated changes in the pharmacokinetics of a particular drug cannot be translated to others. Although clinical studies exploring the effect of diabetes on pharmacodynamics are still very limited, there is evidence that disease-mediated effects are not limited only to pharmacokinetics but also alter pharmacodynamics. However, for many drugs it remains unclear whether these influences reflect diabetes-mediated changes in pharmacokinetics rather than pharmacodynamics. In addition, even though diabetes-mediated pharmacokinetics and pharmacodynamics might be anticipated, it is important to study the effect on each drug and not generalize from observed data. The available data indicate that there is a significant variability in drug response in diabetic subjects. The discrepancies between individual clinical studies as well as between ex vivo and clinical studies are probably due to (i) the restricted and focused population of subjects in clinical studies; (ii) failure to consider type, severity and duration of the disease; (iii) histopathological characteristics generally being missing; and (iv) other factors such as varying medication use, dietary protein intake, age, sex and obesity. The obesity epidemic in the developed world has also inadvertently influenced the directions of pharmacological research. This review attempts to map new information gained since Gwilt published his paper in Clinical Pharmacokinetics in 1991. Although a large body of research has been conducted and significant progress has been made, we still have to conclude that the available information regarding the effect of diabetes on pharmacokinetics and pharmacodynamics remains unclear and further clinical studies are required before we can understand the clinical significance of the effect. An understanding of diabetes-mediated changes as well as of the source of the variability should lead to the improvement of the medical management and clinical outcomes in patients with this widespread disease.

journal_name

Clin Pharmacokinet

authors

Dostalek M,Akhlaghi F,Puzanovova M

doi

10.2165/11631900-000000000-00000

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

481-99

issue

8

eissn

0312-5963

issn

1179-1926

pii

1

journal_volume

51

pub_type

杂志文章,评审
  • A new microemulsion formulation of cyclosporin: pharmacokinetic and clinical features.

    abstract::Cyclosporin (cyclosporin A) has been used as an immunosuppressive agent after organ transplantation for more than 15 years. The bioavailability of cyclosporin in its conventional oral formulation 'Sandimmun' displays considerable inter- and intra-patient variability. Absorption is also bile dependent. Recently, a new ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199630030-00001

    authors: Friman S,Bäckman L

    更新日期:1996-03-01 00:00:00

  • Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis.

    abstract:BACKGROUND:Tildrakizumab is an anti-interleukin-23p19 monoclonal antibody recently approved for the treatment of chronic plaque psoriasis. METHODS:This analysis characterizes the population pharmacokinetics of subcutaneous tildrakizumab and identifies covariates influencing exposure in 2098 healthy volunteers and subj...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,随机对照试验

    doi:10.1007/s40262-019-00743-7

    authors: Jauslin P,Kulkarni P,Li H,Vatakuti S,Hussain A,Wenning L,Kerbusch T

    更新日期:2019-08-01 00:00:00

  • Renal elimination of amikacin and the aging process.

    abstract:OBJECTIVE:Although amikacin is primarily eliminated via glomerular filtration, drug concentrations are not consistently predicted in all patients. To better describe the relationship between amikacin clearance and both age and renal function, we used a new heuristic approach involving statistical analysis of dependence...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-200140120-00004

    authors: Ducher M,Maire P,Cerutti C,Bourhis Y,Foltz F,Sorensen P,Jelliffe R,Fauvel JP

    更新日期:2001-01-01 00:00:00

  • Pharmacology of anticancer drugs in the elderly population.

    abstract::Modifications to bodily functions and physiology are known to occur with age. These changes can have a considerable impact on the pharmacokinetic processes of absorption, distribution, metabolism and excretion and the pharmacodynamic properties of administered drugs. For many drugs with a high therapeutic index, this ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200342140-00003

    authors: Wildiers H,Highley MS,de Bruijn EA,van Oosterom AT

    更新日期:2003-01-01 00:00:00

  • Mass balance studies, with a focus on anticancer drugs.

    abstract::The importance of in-depth knowledge about the pharmacokinetics of a drug is evident because pharmacokinetic behaviour may correlate with activity and toxicity. The most elaborate pharmacokinetic investigation is a so-called mass balance study employing a radioactive tracer. A mass balance study investigates the plasm...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200645010-00003

    authors: Beumer JH,Beijnen JH,Schellens JH

    更新日期:2006-01-01 00:00:00

  • Clinical pharmacokinetics of the salicylates.

    abstract::The use of salicylates in rheumatic diseases has been established for over 100 years. The more recent recognition of their modification of platelet and endothelial cell function has lead to their use in other areas of medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral admin...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198510020-00004

    authors: Needs CJ,Brooks PM

    更新日期:1985-03-01 00:00:00

  • Clinical pharmacokinetics of mifepristone.

    abstract::Mifepristone is a steroidal antiprogestin and antiglucocorticoid acting at the receptor level. The aromatic dimethylaminophenyl side chain in position 11 of the steroid structure is essential for the antagonistic properties of mifepristone. The pharmacokinetics of mifepristone are characterised by rapid absorption, a ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-199733010-00002

    authors: Heikinheimo O

    更新日期:1997-07-01 00:00:00

  • Patient-controlled analgesic therapy, Part III: pharmacokinetics and analgesic plasma concentrations of ketobemidone.

    abstract::The effects of anaesthesia and surgery on the pharmacokinetics of ketobemidone were studied in 12 patients. Plasma ketobemidone concentrations were assayed with a mass-fragmentographic method. The peroperative Vd(area) was 5.9 +/- 2.6L/kg and the terminal half-life was 3.9 +/- 1.7 h. In the postoperative period Vd(are...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-198207030-00005

    authors: Tamsen A,Bondesson U,Dahlström B,Hartvig P

    更新日期:1982-05-01 00:00:00

  • Pharmacokinetic optimisation of vancomycin therapy.

    abstract::Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and concentration-response relationships. No definitive data exist that correlate vancomycin serum concentrations with clinical outcomes. However, inconsistencies ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199528040-00005

    authors: Leader WG,Chandler MH,Castiglia M

    更新日期:1995-04-01 00:00:00

  • Fundamentals of population pharmacokinetic modelling: validation methods.

    abstract::Population pharmacokinetic modelling is widely used within the field of clinical pharmacology as it helps to define the sources and correlates of pharmacokinetic variability in target patient populations and their impact upon drug disposition; and population pharmacokinetic modelling provides an estimation of drug pha...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.1007/BF03261932

    authors: Sherwin CM,Kiang TK,Spigarelli MG,Ensom MH

    更新日期:2012-09-01 00:00:00

  • Pharmacodynamic Analysis of Morphine Time-to-Remedication Events in Infants and Young Children After Congenital Heart Surgery.

    abstract:OBJECTIVE:The aim of this study was to characterize the relationship between morphine plasma concentration and repeated time to postoperative remedication events in children undergoing cardiac surgery. METHODS:Data from our previously published study of morphine pharmacokinetics were utilized in this pharmacodynamic s...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-016-0398-z

    authors: Elkomy MH,Drover DR,Galinkin JL,Hammer GB,Glotzbach KL

    更新日期:2016-10-01 00:00:00

  • Concentration-effect analysis of antihypertensive drug response. Focus on calcium antagonists.

    abstract::Although individualised antihypertensive therapy is widely recommended, prospective methods for optimising treatment are hampered by the paucity of basic information about dose-plasma concentration-response relationships for commonly used drugs. Concentration-effect analysis has been applied to a number of therapeutic...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199426060-00005

    authors: Donnelly R,Elliott HL,Meredith PA

    更新日期:1994-06-01 00:00:00

  • Differences in cytochrome p450-mediated pharmacokinetics between chinese and caucasian populations predicted by mechanistic physiologically based pharmacokinetic modelling.

    abstract:BACKGROUND:International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines emphasize the need for better understanding of the influence of ethnicity on drug response to minimize duplication of clinical studies, thereby expediting drug approval. OBJ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-013-0089-y

    authors: Barter ZE,Tucker GT,Rowland-Yeo K

    更新日期:2013-12-01 00:00:00

  • The relationship between fluticasone furoate systemic exposure and cortisol suppression.

    abstract:INTRODUCTION:The inhaled corticosteroid (ICS) fluticasone furoate is in development, in combination with the long-acting beta2-agonist vilanterol for the once-daily treatment of asthma and chronic obstructive pulmonary disease and as a monotherapy treatment for asthma. Corticosteroids, including ICSs, have the potentia...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,meta分析

    doi:10.1007/s40262-013-0078-1

    authors: Allen A

    更新日期:2013-10-01 00:00:00

  • Pharmacokinetic drug interactions with anti-ulcer drugs.

    abstract::The safety profile of any pharmacological agent is defined on the basis of its toxicity, tolerability and potential for pharmacokinetic and/or pharmacodynamic interactions with other compounds, which may belong to the same or to a different pharmacological class. Drug-drug interactions are important in clinical practi...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199835020-00003

    authors: Negro RD

    更新日期:1998-08-01 00:00:00

  • Comparison of the pharmacokinetics of cephradine and cefazolin in pregnant and non-pregnant women.

    abstract::The pharmacokinetics of cephradine, a cephalosporin with a low degree of protein binding, was studied in 12 women after oral and intravenous administration of the drug during and after pregnancy. Six of the 12 women also received a cephalosporin with a high degree of protein binding, cefazolin, intravenously during an...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-198712020-00004

    authors: Philipson A,Stiernstedt G,Ehrnebo M

    更新日期:1987-02-01 00:00:00

  • Semi-Mechanistic Model for Predicting the Dosing Rate in Children and Neonates for Drugs Mainly Eliminated by Cytochrome Metabolism.

    abstract:BACKGROUND AND OBJECTIVE:A simple approach is proposed to predict drug clearance in children when no paediatric data are available for drugs metabolised by cytochromes. METHODS:The maturation functions of cytochrome activity and binding proteins in plasma were combined with several measures of body size to describe dr...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-017-0596-3

    authors: Cerruti L,Bleyzac N,Tod M

    更新日期:2018-07-01 00:00:00

  • Formation of active metabolites of anticonvulsant drugs. A review of their pharmacokinetic and therapeutic significance.

    abstract::All of the commonly used anticonvulsants drugs, except possibly primidone, are cleared from the human body mainly by metabolism. The metabolites of phenytoin, phenobarbital and ethosuximide have so far not been shown to possess significant pharmacological activity. However, carbamazepine-10,11-epoxide, derived from ca...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199121010-00003

    authors: Eadie MJ

    更新日期:1991-07-01 00:00:00

  • Protein binding as a primary determinant of the clinical pharmacokinetic properties of non-steroidal anti-inflammatory drugs.

    abstract::The ability of a wide variety of anionic, cationic, and neutral drugs to bind in a reversible manner to plasma proteins has long been recognised. Non-steroidal anti-inflammatory drugs (NSAIDs) are distinguished as a class by the high degree to which they bind to plasma protein. Plasma protein binding properties are pr...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198712060-00002

    authors: Lin JH,Cocchetto DM,Duggan DE

    更新日期:1987-06-01 00:00:00

  • Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications.

    abstract::Drug-drug, drug-formulation and drug-meal interactions are of clinical concern for orally administered drugs that possess a narrow therapeutic index. This review presents the current status of information regarding interactions which may influence the gastrointestinal (GI) absorption of orally administered drugs. Abso...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199936030-00004

    authors: Fleisher D,Li C,Zhou Y,Pao LH,Karim A

    更新日期:1999-03-01 00:00:00

  • Clinical pharmacokinetics of leflunomide.

    abstract::Leflunomide is the first disease-modifying antirheumatic drug to be approved for rheumatoid arthritis in the past 10 years. Orally administered leflunomide is almost completely converted into its active metabolite A77 1726 (hereafter referred to as M1). M1 displays linear pharmacokinetics at the dosages of leflunomide...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.2165/00003088-200241060-00003

    authors: Rozman B

    更新日期:2002-01-01 00:00:00

  • Cellular and clinical pharmacology of fludarabine.

    abstract::In the past decade, fludarabine has had a major impact in increasing the effectiveness of treatment of patients with indolent B-cell malignancies. This has come about in a variety of clinical circumstances, including use of fludarabine alone as well as in combinations with DNA-damaging agents or membrane-targeted anti...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200241020-00002

    authors: Gandhi V,Plunkett W

    更新日期:2002-01-01 00:00:00

  • Using Population Pharmacokinetic and Pharmacodynamic Analyses of Entecavir in Pediatric Subjects to Simplify Dosing Recommendations.

    abstract:BACKGROUND:Entecavir is an orally administered guanosine nucleoside analog with activity against hepatitis B virus (HBV) polymerase, which is approved for the treatment of chronic hepatitis B (CHB) infection in adults and children ≥2 years old (USA and EU). OBJECTIVE:To develop simplified entecavir dosing recommendati...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-016-0420-5

    authors: Chan P,Mould DR,Tarif MA,Reynolds L,LaCreta F,Bertz R,Bifano M

    更新日期:2016-12-01 00:00:00

  • Population Pharmacokinetic Analysis of Daclatasvir in Subjects with Chronic Hepatitis C Virus Infection.

    abstract:BACKGROUND AND OBJECTIVE:Daclatasvir is a potent, pangenotypic once-daily hepatitis C virus (HCV) NS5A inhibitor that is approved for the treatment of chronic HCV infection. The objective of this analysis was to characterize the pharmacokinetics of daclatasvir in subjects with chronic HCV infection. METHODS:A populati...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章

    doi:10.1007/s40262-016-0504-2

    authors: Chan P,Li H,Zhu L,Bifano M,Eley T,Osawa M,Ueno T,Hughes E,Bertz R,Garimella T,AbuTarif M

    更新日期:2017-10-01 00:00:00

  • Clinical pharmacokinetics of drugs for Alzheimer's disease.

    abstract::Pharmacological treatment of patients with Alzheimer's disease is becoming more important, as evidenced by the number of drugs being developed in different countries. It has been shown in the majority of clinical trials that cholinesterase inhibitors, such as tacrine (tetrahydroaminoacridine), are able to induce benef...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199529020-00005

    authors: Parnetti L

    更新日期:1995-08-01 00:00:00

  • Clinical pharmacokinetics of metformin.

    abstract::Metformin is widely used for the treatment of type 2 diabetes mellitus. It is a biguanide developed from galegine, a guanidine derivative found in Galega officinalis (French lilac). Chemically, it is a hydrophilic base which exists at physiological pH as the cationic species (>99.9%). Consequently, its passive diffusi...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/11534750-000000000-00000

    authors: Graham GG,Punt J,Arora M,Day RO,Doogue MP,Duong JK,Furlong TJ,Greenfield JR,Greenup LC,Kirkpatrick CM,Ray JE,Timmins P,Williams KM

    更新日期:2011-02-01 00:00:00

  • Desloratadine demonstrates dose proportionality in healthy adults after single doses.

    abstract:OBJECTIVE:To evaluate the dose proportionality and linearity and pharmacokinetic profile of desloratadine after single oral doses over the range of 5 to 20mg. DESIGN:Single centre, randomised, open-label, 4-way crossover study in which healthy adults received single doses of desloratadine (5, 7.5, 10 and 20mg) in 4 di...

    journal_title:Clinical pharmacokinetics

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.2165/00003088-200241001-00001

    authors: Gupta S,Banfield C,Affrime M,Marco A,Cayen M,Herron J,Padhi D

    更新日期:2002-01-01 00:00:00

  • Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs.

    abstract::Consistent with its highest abundance in humans, cytochrome P450 (CYP) 3A is responsible for the metabolism of about 60% of currently known drugs. However, this unusual low substrate specificity also makes CYP3A4 susceptible to reversible or irreversible inhibition by a variety of drugs. Mechanism-based inhibition of ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-200544030-00005

    authors: Zhou S,Yung Chan S,Cher Goh B,Chan E,Duan W,Huang M,McLeod HL

    更新日期:2005-01-01 00:00:00

  • Is there a concentration-effect relationship for sulphonylureas?

    abstract::Sulphonylureas have remained the mainstay of oral therapy for type 2 (non-insulin-dependent) diabetes mellitus (NIDDM). They stimulate insulin release from pancreatic beta cells. Pharmacokinetic differences between the various sulphonylureas are of clinical importance in terms of the time to onset of action, timing of...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-199834030-00001

    authors: Melander A,Donnelly R,Rydberg T

    更新日期:1998-03-01 00:00:00

  • Principles of drug biodisposition in the neonate. A critical evaluation of the pharmacokinetic-pharmacodynamic interface (Part I).

    abstract::Rational pharmacotherapy is dependent upon an understanding of the clinical pharmacokinetic and pharmacodynamic properties of the drugs employed. Although the available data on drug biodisposition and action in the neonate have increased considerably in the last few years, pharmacokinetic-pharmacodynamic interactions ...

    journal_title:Clinical pharmacokinetics

    pub_type: 杂志文章,评审

    doi:10.2165/00003088-198814040-00001

    authors: Besunder JB,Reed MD,Blumer JL

    更新日期:1988-04-01 00:00:00