Plasma pharmacokinetics

KUby JM, Lalezari JP, Eron JJ, Carlson M, Cohen C, Arduino RC, Goodgame JC, Gallant JE, Volberding P, Murphy RL, Valentine F, Saag MS, Nelson EL, Sista PR, Dusek A (2002) The safety, plasma pharmacokinetics, and antiviral activity of subcutaneous enfuvirtide (T-20), a peptide inhibitor of gp41-mediated virus fusion, in HIV-infected adults. AIDS Res Hum Retroviruses 18 685-693... 

Poduslo JF, Curran GL, Gill JS. Pu-trescine-modified nerve growth factor bioactivity, plasma pharmacokinetics, blood-brain/nerve barrier permeability and nervous system biodistribution. 

Based on rat neuropharmacokinetic concepts, it has been proposed [37,42,45] that Cb/U may be projected directly from Cp for large animal species (i.e., dog, monkey, and human) in which Cb are rarely measured. For such species, in which serial blood sampling is common for determining plasma pharmacokinetics, compound Cb,u may be extrapolated using its Cp, species-specific /u,p, and rat-derived Cb,u CP/U assuming a fixed ratio across species ... 

Relating the Time-Course of Plasma Concentrations to the Time-Course of Effect A critical decision to be made after the first human study is whether the compound s speed of onset and duration of action are likely to be consistent with the desired clinical response. Speed of onset is clearly of interest for treatments which are taken intermittently for symptoms rehef, for example, acute treatments for migraine, analgesics, or antihistamines for hay fever. Duration of action phase I is particularly important when the therapeutic effect needs to be sustained continuously, such as for anticonvulsants. The first information on the probable time course of action often comes from the plasma pharmacokinetic profile. However, it has become increasingly evident that the kinetic profile alone may be misleading, with the concentration-time and the effect-time curves being substantially different. Some reasons for this, with examples, include... 

Li, A. C. Alton, D. Bryant, M. S. Shou, W. Z. Simultaneously quantifying parent drugs and screening for metabolites in plasma pharmacokinetic samples using selected reaction monitoring information-dependent acquisition on a QTrap instrument. Rupid Commun Mass Spectrom 2005, 19, 1943-1950. 

Fig. 11. Rabbit plasma pharmacokinetic curves for P743 and the non-specific agent iobitridol for a 120-minute period. From Idee et al. (2001) Invest Radiol 26 41, with permission ( Lippin-cott Williams Wilkins)...

Holleran, J.L. et al. (2005) Plasma pharmacokinetics, oral bioavailabihty, and interspecies scaling of the DNA melhyltransferase inhibitor, zebularine. Clinical Cancer Research, 11, 3862-3868. 

Pharmacology Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), which alters the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor (such as carbidopa), plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. 

LePage GA, Whitecar JP. Pharmacology of 6-thioguaninc in man. Cancer Res 1971 31 1627-1631. Konits PH, Egorin MJ, Van Echo DA et al. Phase II evaluation and plasma pharmacokinetics of high-dose intravenous 6-thioguanine in patients with colorectal carcinoma. Cancer Chemother Pharmacol 1982 8 199-203. 

Maring JG, Oonq BN, de Vries EG. Plasma pharmacokinetics of uracil after an oral uracil challenge dose for dihydropyrimidine dehydrogenase (DPD) phenotyping. Asco Annual Meeting Proceedings J Clin Oncol 2004 22 2120. 

Fox E, Murphy RF, McCully CL, Adamson PC. Plasma pharmacokinetics and cerebrospinal fluid penetration of hypericin in nonhuman primates. Cancer Chemother Pharmacol 2001 47 41-44. 

Chidgey, M.A. J. Caldwell, J. (1986) Studies on benzyl acetate. 1. Effect of dose size and vehicle on the plasma pharmacokinetics and metabolism of fzzzei /zv/cz7c-> C]benzyl acetate in the rat. Food chem. Toxicol., 24, 1257-1265... 

Pannuti, F., C. M. Camaggi, E. Strocchi, and R. Comparsi (1987). Medroxyprogesterone acetate plasma pharmacokinetics after intravenous administration to rabIStacer Chemother. Pharmacol., 19 311-314. 

Tucker, C.E., Chen, L.S., Judkins, M.B., Farmer, J.A., Gill, S.C. and Drolet, D.W. (1999) Detection and plasma pharmacokinetics of an anti-vascular endothelial growth factor oligonucleotide-aptamer (NX 1838) in rhesus monkeys. J. Chromatogr. B., 732, 203-212. 

V. Borek-Dohalsky, J. Huclova, B. Barrett, B. Nemec, I. Ulc, I. Jelinek, Validated HPLC-MS-MS method for simultaneous determination of atorvastatin and 2-hydroxyatorvas-tatin in human plasma-pharmacokinetic study, Anal. Bioanal. Chem. 386 (2006) 275-285. 

Gardana C, Guamieri S, Riso P, Simonetti P and Porrini M, Flavanone plasma pharmacokinetics from blood orange juice in human subjects. Brit J Ntilr 98 165-172 (2007). 

Egorin, M.J., Yuan, Z-M., Sentz, D.L., Plaisance, K., Eiseman, J.L. 1999. Plasma pharmacokinetics of butyrate after intravenous administration of sodium butyrate or oral administration of tributyrin or sodium butyrate to mice and rats. Cancer Chemother. Pharmacol. 43, 445-453. 

Plasma Pharmacokinetic Parameters of md-LErafAON in PC-3 Tumor-Bearing Balb/c nu/nu Mice After Single i.v. Dose of 30 mg/kg... 

Plasma pharmacokinetic parameters are assessed by standard methods (11-13,29). 

In summary, the plasma pharmacokinetic profile of XYZ123 is similar to that achieved in healthy subjects... 

Arnold, R. D., Mager, D. E., Slack, J. E., and Straubinger, R. M. (2005), Effect of repetitive administration of Doxorubicin-containing liposomes on plasma pharmacokinetics and drug biodistribution in a rat brain tumor model, Clin. Cancer Res., 11, 8856-8865. 

In rats, caspofungin did not alter the plasma pharmacokinetics of ketoconazole, a potent inhibitor of CYP3A4 (5). Co-administration of caspofungin 50 mg/ day and itraconazole 200 mg/day to healthy subjects for 14 days did not alter the pharmacokinetics of either drug (15). 

In rats, caspofungin did not alter the plasma pharmacokinetics of indinavir, a substrate and competitive inhibitor of CYP3A2 (5). 

While tacrolimus had no effect on the plasma pharmacokinetics of caspofungin, chronic caspofungin reduced the AUC of tacrolimus by about 20% (5). 

The effect of fluconazole on the plasma pharmacokinetics of doxorubicin has been investigated in a randomized, crossover study in non-human primates (94). Fluconazole (10 mg/kg/day) was given intravenously for 4 days before doxorubicin (2.0 mg/kg intravenously). Pretreatment with fluconazole had no effect on the pharmacokinetics of doxorubicin, and the incidence of severe neutropenia (absolute neutrophil count below 0.5 X 10 / 1) was higher with doxorubicin alone than with the combination of doxorubicin and fluconazole. Thus, fluconazole does not appear to contribute to the marrow-suppressive effects of doxorubicin. 

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