Practical pharmacokinetics: what do you really need to know?

Starkey, Elizabeth; Sammons, Helen

doi:10.1136/archdischild-2013-304555

Cited by 15 publications

(7 citation statements)

References 26 publications

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“…Intravenous (i.v.) pharmacokinetic (PK) studies are the initial step in determining if a drug has systemic distribution and bioavailability in a particular species 15,16 . The primary objective of this study was to determine the noncompartmental i.v.…”

Section: Introductionmentioning

confidence: 99%

Noncompartmental pharmacokinetics of three intravenous mycophenolate mofetil concentrations in healthy Standardbred mares

Burroughs

Lorch

Guo

et al. 2022

Veterinary Dermatology

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Background: Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA) which acts as an immunosuppressive agent. During the biotransformation of MMF to MPA, additional metabolites including MPA phenol glucuronide (MPAG), MPA acyl glucuronide (AcMPAG) and MPA phenol glucoside (MPG) are formed. Objective: To define the noncompartmental pharmacokinetic (PK) parameters of three single doses of intravenous (i.v.) MMF and its downstream metabolites in healthy horses. Animals: Six healthy Standardbred mares. Materials and Methods: Generic MMF (Par Pharmaceuticals; Chestnut Ridge, NY, USA) was reconstituted and administered as a single i.v. bolus at 1.0 mg/kg, 5.0 mg/kg and 10.0 mg/kg with an eight day washout between treatments. Blood samples were collected immediately before MMF administration and over 24 h. A liquid chromatography-tandem mass spectrometry assay was developed following FDA guidance to determine plasma MMF, MPA, MPAG, AcMPAG and MPG concentrations. Plasma concentrations were analysed independently, followed by calculation of geometric mean and coefficient of variation. Results: Noncompartmental PK parameters were determined for MMF and all metabolites at all doses. MMF was rapidly converted to MPA in all horses. Each incremental dose of MMF resulted in increases in C max and AUC inf _ obs for MPA and the three additional metabolites. Within the 10-fold dose range, the increase in C max and AUC inf _obs for MMF and its metabolites was nonlinear. Conclusions and clinical relevance: Horses biotransform MMF into MPA, MPAG, AcMPAG and MPG via the glucuronidation and glucosidation clearance pathways. Equine reference PK profiles for MPA and the metabolites, MPAG, AcMPAG and MPG were established.

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Section: Introductionmentioning

confidence: 99%

Noncompartmental pharmacokinetics of three intravenous mycophenolate mofetil concentrations in healthy Standardbred mares

Burroughs

Lorch

Guo

et al. 2022

Veterinary Dermatology

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“…[3] However, off-label dosing recommendations for currently marketed drugs need to be revisited, [1,[4][5][6][7][8] especially for older, off-patent medications. [7] Given the general lack of interest in the 'paediatric-use marketing authorisation' opportunity, which provides sponsors incentives for research on off-patent drugs, the initiative to gather empirical evidence to support the dose rationale for older drugs is left to non-commercial (academic) paediatric clinicianscientists. [9] In fact, the need for increasing awareness of paediatricians about the value of investigator-initiated trials in children is acknowledged in the revision of Directive of the European Commission (EC) in 2014, which tries to correct the bias towards trials sponsored by pharmaceutical companies, 'while those with non-commercial sponsors were overlooked'.…”

Section: Introductionmentioning

confidence: 99%

“…Sponsors can submit a paediatric investigation plan to support the authorisation of a new drug for children . However, off‐label dosing recommendations for currently marketed drugs need to be revisited, especially for older, off‐patent medications . Given the general lack of interest in the ‘paediatric‐use marketing authorisation’ opportunity, which provides sponsors incentives for research on off‐patent drugs, the initiative to gather empirical evidence to support the dose rationale for older drugs is left to non‐commercial (academic) paediatric clinician‐scientists .…”

Section: Introductionmentioning

confidence: 99%

How to optimise drug study design: pharmacokinetics and pharmacodynamics studies introduced to paediatricians

Vermeulen

Anker

Pasqua

et al. 2017

Journal of Pharmacy and Pharmacology

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ObjectivesIn children, there is often lack of sufficient information concerning the pharmacokinetics (PK) and pharmacodynamics (PD) of a study drug to support dose selection and effective evaluation of efficacy in a randomised clinical trial (RCT). Therefore, one should consider the relevance of relatively small PKPD studies, which can provide the appropriate data to optimise the design of an RCT.MethodsBased on the experience of experts collaborating in the EU‐funded Global Research in Paediatrics consortium, we aimed to inform clinician‐scientists working with children on the design of investigator‐initiated PKPD studies.Key findingsThe importance of the identification of an optimal dose for the paediatric population is explained, followed by the differences and similarities of dose‐ranging and efficacy studies. The input of clinical pharmacologists with modelling expertise is essential for an efficient dose‐finding study.ConclusionsThe emergence of new laboratory techniques and statistical tools allows for the collection and analysis of sparse and unbalanced data, enabling the implementation of (observational) PKPD studies in the paediatric clinic. Understanding of the principles and methods discussed in this study is essential to improve the quality of paediatric PKPD investigations, and to prevent the conduct of paediatric RCTs that fail because of inadequate dosing.

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“…Metabolism can alter the structure of a molecule, reducing its function or completely stopping its function. It can also produce a functioning molecule from an inactive compound (such as prodrugs) [ 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Potential Pharmacokinetic Interactions of Common Cardiovascular Drugs and Selected European and Latin American Herbal Medicines: A Scoping Review

Prieto

Graham

Alkhabbaz

et al. 2023

Plants

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Background: Herb–drug interactions are nowadays an important decision factor in many healthcare interventions. Patients with cardiovascular risk factors such as hyperlipidemia and hypertension are usually prescribed long-term treatments. We need more informed decision tools to direct future clinical research and decision making to avoid HDI occurrences in this group. Methods: A scoping review was conducted using data from online databases such as PUBMED, the National Library of Medicine, and the electronic Medicines Compendium. Included studies consisted of the reported effects on Phase 1/2 and P-glycoprotein of herbal medicines listed in the medicines agencies of Latin America and Europe and drugs used for cardiovascular conditions (statins, diuretics, beta blockers, calcium channel blockers, and ACE inhibitors). The cross tabulation of the results allowed for finding potential HDI. Results and conclusions: as per the preclinical data reviewed here, we encourage more clinical research on whether drugs with apparently very low interaction risk, such as pravastatin, nadolol, and nimodipine/nitrendipine, may help prevent HDI when statins, beta blockers, and calcium channel blockers, respectively, are prescribed for long-term treatments.

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Practical pharmacokinetics: what do you really need to know?

Cited by 15 publications

References 26 publications

Noncompartmental pharmacokinetics of three intravenous mycophenolate mofetil concentrations in healthy Standardbred mares

Noncompartmental pharmacokinetics of three intravenous mycophenolate mofetil concentrations in healthy Standardbred mares

How to optimise drug study design: pharmacokinetics and pharmacodynamics studies introduced to paediatricians

Potential Pharmacokinetic Interactions of Common Cardiovascular Drugs and Selected European and Latin American Herbal Medicines: A Scoping Review

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