Pharmacokinetics pharmacodynamic correlations

H. Derendorf and G. Hochhaus, Handbook of Pharmacokinetic / Pharmacodynamic Correlation, CRC Press, Boca Raton, FL, 1995. 

Cortes JE et al (2009) Pharmacokinetic/pharmacodynamic correlation and blood-level testing in imatinib therapy for chronic myeloid leukemia. Leukemia 23 1537-1544... 

It was found that pharmacokinetic-pharmacodynamic correlation in mice demonstrated that plasma concentrations of > 40 pmol/L after pazopanib (30 mg/kg p.o.) inhibited VEGF-induced VEGFR2 phosphorylation for more than 8 h. The mean plasma concentrations were 153.9,47.5,41.1, 17.4, and 4.3 pmol/L at times of 1,4, 8, 16, and 24 h. 

Derendorf, H. and Hochhaus, G., Handbook of Pharmacokinetic/Pharmacodynamic Correlation, CRC, 1995. 

Pharmacokinetic-pharmacodynamic correlations between AUC, response rates, and the extent of myelosuppression have been examined retrospectively in patients with advanced ovarian carcinoma (21,24). AUC values below 4 minutes/mg/ml and exceeding 7 minutes/mg/ml cannot be recommended the former is associated with low response rates and the latter is associated with more pronounced neutropenia and thrombocytopenia without higher response rates. Doses of carboplatin are generally calculated by the Calvert formula (26) ... 

Della Paschoa OE, Hoogerkamp A, Edelbroek PM, Voskuyl RA, Danhof M. Pharmacokinetic-pharmacodynamic correlation of lamotrigine, flunarizine, loreclezole, CGP40116 and CGP39551 in the cortical stimulation model. Epilepsy Res 2000 40 41-52. 

Pharmacokinetic/pharmacodynamic model using nonlinear, mixed-effects model in two compartment, best described time course of concentration strong correlation with creatinine clearance predicted concentration at the efi ect site and in reduction of heart rate during atrial fibrillation using population kinetic approach... 

This section deals with the question of whether there are quantitatively detectable and interpretable correlations between the dose of an administered drug, or the concentration of a drug and its metabolites measured in the blood or plasma (blood or plasma level), and the therapeutic action or side effects observed. Investigations relating to questions of this type are called PK PD (pharmacokinetic pharmacodynamic) studies. The PK PD analysis is a bidirectional approach pharmacokinetics represent what the body does with a drug, and pharmacodynamics describes what a drug does to the body. The PK PD analyses are key elements of early drug development, and PK PD trials are able to answer specific disease-related efficacy and safety questions. 

Therefore, this review of pharmacokinetic/pharmacodynamics (PK/PD) correlation will include investigations between the effective concentrations at the target sites of antisense oligonucleotides with each of the pharmacological effects discussed above. Moreover, an establishment of the correlation between plasma equilibrium concentrations with concentrations at the target sites is pertinent, enabling plasma concentrations to be used as a surrogate in clinical studies to establish relationships between pharmacodynamics and pharmacokinetics. 

Cox, E.H. et al. Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of synthetic opioids in the rat correlation with the interaction at the mu-opioid receptor. J Pharmacol Exp Ther 1998, 284 1095-1103. 

MandemaJW, SansomLN, Dios-VieitezMC, etal. Pharmacokinetic-pharmacodynamic modeling of the electroencephalographic effects of benzodiazepines. Correlation with receptor binding and anticonvulsant activity. / Pharmacol Exp Ther. 1991 257(l) 472-478. 

Obach RS. 1996a. Prediction of human pharmacokinetics using in vitro-in vivo correlations . In Pharmacokinetic/Pharmacodynamic Analysis ... 

Since dose tolerance studies usually produce adverse events, pharmacokinetic evaluation should include an assessment of the dose-concentration-toxicity relationship. In addition to regularly scheduled plasma samples obtained to calculate pharmacokinetic parameters, it is common to obtain a plasma sample at the time an adverse event is observed. Often it is possible to correlate acute toxicity with plasma concentrations as well as with dose, and occasionally even to develop a pharmacokinetic/pharmacodynamic model for acute or subchronic toxicity. 

Belani CP, Kearns CM, Zuhowski EG, Erkmen K, Hiponia D, Zacharski D, Engstrom C, Ra-manathan RK, Capozzoli MJ, Aisner J, Egorin MJ. Phase I trial, including pharmacokinetics and pharmacodynamic correlations, of combination paclitaxel and carboplatin in patients with metastatic non-small-cell lung cancer, 7 Oncol 999) 17, 676-84. 

Calculated molecular properties from 3D molecular fields of interaction energies are a novel approach to correlate 3D molecular structures with pharmacodynamic, pharmacokinetic and physico-chemical properties. The novel VolSurf descriptors quantitatively characterize size, shape, polarity, hydrophobicity and the balance between them. 

IV iron preparations have different pharmacokinetic profiles, which do not correlate with pharmacodynamic effect. 

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