Pharmaco-kinetics

L. Hendeles, R. Iafrate, and M. Weinberger, A clinical and pharmacokinetic basis for the selection and use of slow release theophylline products, Clin. Pharmaco-kinet, 9, 95 (1984). 

Absorption, distribution, metabolism, and excretion/pharmaco-kinetics... 

Ames, M.M., Powin, G., and Kovach, J. S. (1983) Pharmaco kinetics of anticancer agents in humans, Elsevier, Amsterdam, New York, Oxford. 

Burman WJ, Gallicano K, Peloquin C Comparative pharmacokinetics and pharmacodynamics of the rifamycin antibiotics. Clin Pharmaco-kinet 2001 40 327-341. 

Cardot JM, Beyssac E. In vitro/in vivo correlations scientific implications a standardisation. Eur J Drug Metab Pharmaco-kinet 1993 18(1) 113—120. 

Hall MG Wilks ME, Provan WM, Eksborg S, Lumholtz B. (2001) Pharmaco-kinetics and pharmacodynamics of NTBC [2-(2-nitro-4-fluo-romethyl-benzoyl)-l,3-cyclohexanedione] and mesotrione, inhibitors of 4-hydroxyphenyl pyruvate dioxygenase (HPPD) following a single dose to healthy male volunteers. Br J Clin Pharmacol 52 169-177. 

The kidney disease affects the pharmaco-kinetics of certain drugs. 

Ten of the 20 pesticides known to be teratogenic (Table 20) in animals are OPPs (starred). None is listed for teratologic studies in the latest published NTP Annual Plan and NTP Review of the National Toxicology Program (1986). A few, including Parathion are scheduled for neuro-behavioral, and/or pharmaco-kinetic/metabolism studies, but at relatively low (D) priority (ref. 172a,b). 

Pharmaco-kinetic 24 hrs and 1 month Preloaded OC stent 0.37(12) (1 (xCi radio-labeled batimastat 14C per stent) 9 New Zealand white rabbits... 

Ameer B, Weintraub RA. Drug interactions with grapefruit juice. Clin Pharmaco-kinet 1997 33 103-121. 

Helsby NA, Ward SA, Edwards G, et al. The pharmaco-kinetics and activation of proguanil in man consequences of variability in drug metabolism. Br J Clin Pharmacol 1990 30 593-598. 

V. V. Estimation of population characteristics of pharmacokinetic parameters from routine clinical data. J Pharmaco-kinet Biopharm 1977, 5 445—479. 

MODIFICATION OF THE METHOD Modification should be considered according to the pharmaco-kinetic behavior of the drag substance. 

In recent years studies have been developed in spontaneous disease models, gene knock out models and transgenic animals. These models provide information on the pharmacological action, pharmaco-kinetics and tolerability of a biotech products. 

The route of administration should be the same or as close as possible to that proposed for clinical use. As in the case of heterocyclic chemicals, pharmaco-kinetic behaviour and bioavailability in the test species should be comparable to humans. In case the product is cleared faster from the test animals than in humans, the frequency of administration in the animals can be increased. 

Because JP-8 is a complex mixture of numerous volatile hydrocarbons and other substances, it is difficult to describe the pharmaco-kinetics both of the mixture and of its components as they relate to toxicity. The pharmacokinetics of some JP-8 components are known, but the usefulness of such data is limited because some components of the mixture likely affect the kinetics of uptake, distribution, metabolism, and elimination of others in the mixture. The kinetics of the mixture also would vary by route (e.g., oral versus dermal) and condition of exposure (e.g., aerosol versus vapor). 

The DART Identification Committee evaluated each selected agent for male and female reproductive toxicity and developmental toxicity in humans and experimental animals. It also reviews other types of available toxicity data (e.g., acute and carcinogenicity) and pharmaco-kinetic data. 

Platinum coordination complexes have been investigated as potential anticancer agents since 1972. The most successful of these is the cis dichlor-diammine platinum(II) complex which is particularly effective for the treatment of ovarian and testicular carcinomas. However, effective therapy requires high doses, typically 4.0/umol (825/ig)kg-1 given intravenously, which produce unpleasant and toxic reactions. Pharmaco-kinetic studies of the various Pt species in plasma indicate that the active species is of low molecular weight and the protein bound Pt species is apparently inactive [106]. Further work is needed to identify the active species and to develop therapeutic procedures that produce maximum anti-tumour activity with minimum toxicity. 

Note. For a review of the clinical pharmacokinetics of diuretics see B. Beerman and M. Groschinsky-Grind, Clin. Pharmaco-kinet., 1980, 5, 221-245. 

Note. Spectrophotometric and gas chromatographic assays have been shown to be non-selective due to interference from acid-labile hydrazones—see P. A. Reece et al., J. pharm. Sci., 1978, 67, 1150-1153 and T. M. Ludden et al., Clin. Pharmaco-kinet., 1982, 7, 185-205. 

Quantification. Gas Chromatography. In plasma sensitivity 4 ng/ml, AFID—F. Rousseau etal., Eur. J. drug Met. Pharmaco-kinet., 1981,6, 281-288. 

Classic pharmaco-kinetic consideration gives a theoretical steady state plasma concentration equal to production (dosing rate) divided by clearance, i.e. between 0.017 and 0.100 nmol/L. The conventional HPLC-ECD and HPLC-MS/MS methods have sensitivity close to that level. Using up-concentrations and a HPLC-ECD system with a non-commercially available carbon column Bogdanov et al. [19] reported plasma values of 0.014 - 0.070 nmol/L (4- 21 pg/ml), i.e. in close agreement with the theoretical values. 

Harris, J.M. Martin, N.E. Modi, M. Pegylation a novel process for modifying pharmacokinetics. Clin. Pharmaco-kinet. 2001, 40 (7), 539-551. 

Sheiner, L.B. Beal, S.L. Evaluation of methods for estimating population pharmacokinetic parameters. I. Biexponential model and experimental pharmacokinetic data. J. Pharmaco-kinet. Biopharm. 1981, 9 (5), 635-651. 

Lunn, D.J. Best, N. Thomas, A. Wakefield, L Spiegelhalter, D. Bayesian analysis of population PK/ PD models general concepts and software. J. Pharmaco-kinet. Pharmacodyn. 2002, 29 (3), 271-307. 

Gianni L, Kearns CM, Giani A, Capri G, Vigano L, Lacatelli A, Bonadonna G, Egorin MJ. Nonlinear pharmacokinetics and metabolism of paclitaxel and its pharmaco-kinetic/pharmacodynamic relationships in humans. J Clin Oncol 1995 13(l) 180-90. 

Prichard BN, Brogden RN. Xipamide. A review of its pharmacodynamic and pharmaco kinetic properties and therapentic efficacy. Drngs 1985 30(4) 313-32. 

The benzene ring scaffold has advantages of non-chirality, chemical and metabolic stability and increased lipophilicity compared with the dihydropyran ring. These factors may be important to improve the deficient pharmaco-kinetic profiles observed for GG167. 

Pregnancy Pharmaco-kinetic category C Absorbed from the GI tract metabolized in the liver excreted in urine. Crosses the blood-brain barrier and the placenta and is found in breast milk PB 93% not removed by hemodialysis... 

Llerena A, Cobaleda J, Martinez C, et al Interethnic differences in drug metabolism influence of genetic and environmental factors on de-brisoquine hydroxylation phenotype. Eur J Drug Metab Pharmaco-kinet 21 129-138,1996... 

Bergstrom M, Cass LM, Valind S, Westerherg G, Lundherg EL, Gray S, et al. Deposition and disposition of [llC]zanamivir following administration as an intranasal spray. Evaluation with positron emission tomography. Clin Pharmaco-kinet 1999 36(suppl l) 33-39. 

---