A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods

Mahmood, Iftekhar; Yuan, Rae

doi:10.1002/(sici)1099-081x(199904)20:3<137::aid-bdd165>3.0.co;2-i

Cited by 27 publications

(16 citation statements)

References 18 publications

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“…Various methods were utilized to predict CL and Vd ss values of MI-219 in human. The plasma concentration-time profile in humans was also predicted using Dedrick plots and Wajima's method (9)(10)(11)(12).…”

Section: Introductionsupporting

confidence: 86%

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Preclinical Pharmacokinetics of MI-219, a Novel Human Double Minute 2 (HDM2) Inhibitor and Prediction of Human Pharmacokinetics

Zou¹,

Zheng²,

Yu³

et al. 2012

J Pharm Pharm Sci

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-Purpose. The two purposes of this study were evaluating preclinical pharmacokinetics of MI-219 and predicting clearance (CL) and volume of distribution at steady-state (Vd ss ) of MI-219 in humans. Methods. Pharmacokinetic studies were conducted on mice, rats, dogs, and monkeys. Human CL of MI-219 was predicted using allometric scaling (SA), multi-exponential allometric scaling (ME), rule of exponents (RoE), single species scaling, two-term power equation (TTPE), physiologically based in vitro-in vivo extrapolation (IVIVE), and f u corrected intercept method (FCIM). In vitro assays were conducted to determine in vitro intrinsic CL, protein binding, and blood-plasma partition coefficients. To estimate half-life of MI-219, plasma concentration-time profile in humans was predicted using kallynochron and apolysichron time transformation (Dedrick plots) and normalization with MRT and Vd ss (Wajima's method). In addition, simultaneous interspecies scaling of CL, Vd ss and concentration-time profile were performed by using Nonlinear Mixed Effects Modeling (NONMEM). Results. Preclinical studies showed that the elimination of MI-219 was mainly through metabolism. The validation using observed monkey CL and Vd ss showed that MA, IVIVE and Oie-Tozer methods were accurately than the other methods. Human CL of MI-219 predicted by ME and IVIVE was between 0.237-0.342 L*h -1 *kg -1. Human Vd ss predicted by Oie-Tozer method and allometric scaling of unbound volume of distribution of tissues (V T /fu T ) method was between 0.93-1.40 L*kg -1 . Superimposition of rat, monkey and dog data was observed in Dedrick plots and Wajima's transformations. Conclusions. The predicted human pharmacokinetics is useful for the design of first-in-human study.

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Section: Introductionsupporting

confidence: 86%

“…The plasma concentration-time profile of MI-219 in humans (assume an i.v administration of 5mg/kg of MI-219) was simulated by using two Dedrick plot methods (based on Kallynochrons and Apolysichrons) (8,11,22 [19] Apolysichrons:…”

Section: Dedrick Plotsmentioning

confidence: 99%

Preclinical Pharmacokinetics of MI-219, a Novel Human Double Minute 2 (HDM2) Inhibitor and Prediction of Human Pharmacokinetics

Zou¹,

Zheng²,

Yu³

et al. 2012

J Pharm Pharm Sci

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“…Dedrick plots and related modified methods are based on the concept of physiological time, with the concentration-time profile in animals being transformed by correction factors to yield a human profile (24,34). The species-invariant time method is based on the theory that a complex Dedrick plot, with exponents obtained from best fitting of the animal intravenous plasma concentration-time profiles, can generate a human plasma concentration-time profile by correlating variations in biological structure (e.g., blood vessel size) and metabolic rates (e.g., glomerular filtration rate) (34,35). The dose normalized plasma concentrations and time data from preclinical species (e.g., rat, dog, and monkey) were transformed by dividing the dose normalized concentrations (Y axis) and time (X axis) by the body weight to a power.…”

Section: Human Exposure Projectionsmentioning

confidence: 98%

Projection of Exposure and Efficacious Dose Prior to First-in-Human Studies: How Successful Have We Been?

Huang

Zheng²,

Yang

et al. 2007

Pharm Res

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“…In the Dedrick plot using equivalent time, the intravenous plasma concentration-time curve was transformed by dividing the concentrations and time scales of various species by dose (per kilogram of body weight) or W 0.25 , respectively. In the Dedrick plot using kallynochrons, apolysichrons, and dienetichrons as time units, b, c, and d are the allometric scaling exponents of CL, Vd ss , and CL×MLP, respectively (90). The transformed concentration-time curves of various species are superimposed and then backtransformed to estimate human i.v.…”

Section: Species-invariant Time Methods (Dedrick Plots)mentioning

confidence: 99%

Applications of Human Pharmacokinetic Prediction in First-in-Human Dose Estimation

Zou

Zheng

et al. 2012

AAPS J

113

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Abstract. Quantitative estimations of first-in-human (FIH) doses are critical for phase I clinical trials in drug development. Human pharmacokinetic (PK) prediction methods have been developed to project the human clearance (CL) and bioavailability with reasonable accuracy, which facilitates estimation of a safe yet efficacious FIH dose. However, the FIH dose estimation is still very challenging and complex. The aim of this article is to review the common approaches for FIH dose estimation with an emphasis on PK-guided estimation. We discuss 5 methods for FIH dose estimation, 17 approaches for the prediction of human CL, 6 methods for the prediction of bioavailability, and 3 tools for the prediction of PK profiles. This review may serve as a practical protocol for PK-or pharmacokinetic/pharmacodynamic-guided estimation of the FIH dose.

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A comparative study of allometric scaling with plasma concentrations predicted by species-invariant time methods

Cited by 27 publications

References 18 publications

Preclinical Pharmacokinetics of MI-219, a Novel Human Double Minute 2 (HDM2) Inhibitor and Prediction of Human Pharmacokinetics

Preclinical Pharmacokinetics of MI-219, a Novel Human Double Minute 2 (HDM2) Inhibitor and Prediction of Human Pharmacokinetics

Projection of Exposure and Efficacious Dose Prior to First-in-Human Studies: How Successful Have We Been?

Applications of Human Pharmacokinetic Prediction in First-in-Human Dose Estimation

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