Measurement of the renal clearance of drugs.

Tucker, GT

doi:10.1111/j.1365-2125.1981.tb01304.x

Cited by 152 publications

(66 citation statements)

References 45 publications

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“…In the absence of renal metabolism, CL R is determined by a combination of glomerular filtration, active transport into and/ or out of tubular epithelial cells, and passive tubular reabsorption (12). Determining the actual contribution of a given active transport or passive permeability process from typical clinical CL R data represents a substantial challenge, even when data from repeated measurement of drug excretion in short intervals in the urine are available.…”

Section: Renal Drug Disposition As a Results Of Multiple Processesmentioning

confidence: 99%

“…Various mechanistic kidney models have been reported that allow simulation of different processes (filtration, metabolism, transport, passive permeation) individually and in combination. In general, static models typically consider filtration, secretion and/or reabsorption in isolation and as separate mechanisms contributing to overall CL R (11)(12)(13). Conversely, dynamic models that are comprised of compartments representing physiological spaces (e.g.…”

Section: Use Of Models For Studying Pharmacokinetics In Kidney: Currementioning

confidence: 99%

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Key to Opening Kidney for In Vitro-In Vivo Extrapolation Entrance in Health and Disease: Part II: Mechanistic Models and In Vitro-In Vivo Extrapolation

Scotcher

Jones²,

Posada

et al. 2016

AAPS J

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Abstract.It is envisaged that application of mechanistic models will improve prediction of changes in renal disposition due to drug-drug interactions, genetic polymorphism in enzymes and transporters and/or renal impairment. However, developing and validating mechanistic kidney models is challenging due to the number of processes that may occur (filtration, secretion, reabsorption and metabolism) in this complex organ. Prediction of human renal drug disposition from preclinical species may be hampered by species differences in the expression and activity of drug metabolising enzymes and transporters. A proposed solution is bottom-up prediction of pharmacokinetic parameters based on in vitro-in vivo extrapolation (IVIVE), mediated by recent advances in in vitro experimental techniques and application of relevant scaling factors. This review is a follow-up to the Part I of the report from the 2015 AAPS Annual Meeting and Exhibition (Orlando, FL; 25th-29th October 2015) which focuses on IVIVE and mechanistic prediction of renal drug disposition. It describes the various mechanistic kidney models that may be used to investigate renal drug disposition. Particular attention is given to efforts that have attempted to incorporate elements of IVIVE. In addition, the use of mechanistic models in prediction of renal drugdrug interactions and potential for application in determining suitable adjustment of dose in kidney disease are discussed. The need for suitable clinical pharmacokinetics data for the purposes of delineating mechanistic aspects of kidney models in various scenarios is highlighted.KEY WORDS: active renal excretion; human kidney transporters; human renal drug clearance; kidney disease; non-hepatic drug metabolism.

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Section: Renal Drug Disposition As a Results Of Multiple Processesmentioning

confidence: 99%

Section: Use Of Models For Studying Pharmacokinetics In Kidney: Currementioning

confidence: 99%

Key to Opening Kidney for In Vitro-In Vivo Extrapolation Entrance in Health and Disease: Part II: Mechanistic Models and In Vitro-In Vivo Extrapolation

Scotcher

Jones²,

Posada

et al. 2016

AAPS J

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show abstract

“…Slow equilibration is revealed by a rise in plasma drug concentration during the first few hours after the end of dialysis; this has been observed with atenolol for example (Flouvat et al, 1980). Total systemic clearance of drug CL is increased during dialysis by the additional dialyser clearance CL,, This may be calculated from equation 13 which is analogous to equation 1 in Dr Tucker's article (Tucker, 1981) CLD = OD. ED (13) where QD is the rate of flow of plasma through the haemodialysis unit and ED is the extraction ratio (Concentration of drug in arterial plasma less concentration of drug in plasma returning to the patient divided by concentration of drug in arterial plasma).…”

Section: Allowance For Dialysismentioning

confidence: 96%

“…Preliminary experience with single test doses will have indicated whether the first dose D mg must be reduced below the standard adult value either to avoid excessive peak concentrations (Mawer et al, 1972) or to take account of increased target organ sensitivity (Fabre & Balant, 1976 (Documenta Geigy, 1970 (Bjaeldager etal., 1980 (Tucker, 1981). Orme & Cutler (1969) for example showed that CLR (7) kanamycin is proportional to CLR inulin and to CLR creatinine Similarly CLR digoxin is proportional to CLR creatnine (Bloom & Nelp, 1966); digoxin clearance is partly by active secretion (Steiness, 1974).…”

Section: Therapeutic Dosage In Renal Failurementioning

confidence: 99%

Dosage adjustment in renal insufficiency.

Mawer¹

1982

Brit J Clinical Pharma

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“…The problem can be circumvented by using a different approach based on the disappearance from serum of a substance solely eliminated by glomerular filtration. The method is equivalent to the well known way of measuring the clearance of drugs (Tucker, 1981). Early methods used thiosulphate (Vorbruger, Riedwyl & Reubi, 1969) and inulin (Rose, 1969) but the approach gained popularity with the introduction of radiolabelled substances easy to quantitate in plasma.…”

Section: Cr-edta Clearancementioning

confidence: 99%