Intravenous administration pharmacokinetics

Gupta PK, Ehrnebo M. 1979. Pharmacokinetics of alpha isomer and beta isomers of racemic endosulfan following intravenous administration in rabbits. Drug Metab Dispos 7 7-10. 

McMahon B.M., Mays D., Lipsky J., Stewart J.A., Fauq A., Richelson E. Pharmacokinetics and tissue distribution of a peptide nucleic acid after intravenous administration. Antisense Nucleic Acid Drug Dev. 2002 12 65-70... 

Intravenous administration displays a different pharmacokinetic profile than subcutaneous administration... 

Etoposide causes multiple DNA double-strand breaks by inhibiting topoisomerase II. The pharmacokinetics of etoposide are described by a two-compartment model, with an a half-life of 0.5 to 1 hour and a (5 half-life of 3.4 to 8.3 hours. Approximately 30% of the dose is excreted unchanged by the kidney.16 Etoposide has shown activity in the treatment of several types of lymphoma, testicular and lung cancer, retinoblastoma, and carcinoma of unknown primary. The intravenous preparation has limited stability, so final concentrations should be 0.4 mg/mL. Intravenous administration needs to be slow to prevent hypotension. Oral bioavailability is approximately 50%, so oral dosages are approximate two times those of intravenous doses however, relatively low oral daily dosages are used for 1 to 2 weeks. Side effects include mucositis, myelosuppression, alopecia, phlebitis, hypersensitivity reactions, and secondary leukemias. 

N. A., Flink, O., Paalzow, L., Ampicillin comparison of bioavailability and pharmacokinetics after oral and intravenous administration of three brands, Eur. J. Clin. Pharmacol. 1976, 30, 237-243. 

Piel et al. compared the intravenous pharmacokinetics of miconazole in sheep after its administration in a polyoxyl-35 castor oil/lactic acid mixture, a 100 pM hydroxylpropyl-/l-cyclodextrin-50 pM lactic acid solution, and a 50 pM sulfobutyl ether (SBE7)-/i-cyclodextrin 50 pM lactic acid solution. Intravenous administration of 4 mg/kg of miconazole was completed within 5 min [108]. There were no differences of the miconazole blood plasma concentration versus time for the three dosage forms. The half-life of distribution was <2.4 min. Both hydroxylpropyl-/ -... 

Piel et al. [109] studied the pharmacokinetics of miconazole after intravenous administration to six sheep (4 mg/kg) of three aqueous solutions - a marketed micellar solution containing polyoxyl-35 castor oil was compared with two solutions both containing 50 pM lactic acid and a cyclodextrin derivative (100 pM hydro-xylpropyl-/l-cyclodextrin or 50 pM sulfobutyl ether (SBE7)-/i-cyclodextrin. This work demonstrated that these cyclodextrin derivatives have no effect on the pharmacokinetics of miconazole by comparison with the micellar solution. The plasma concentration-time curves have shown that there is no significant difference between the three solutions. 

Ohzawa et al [112] studied the absorption, distribution, and excretion of 14C miconazole in rats after a single administration. After the intravenous administration of 14C miconazole at a dose of 10 mg/kg to the male rats, the plasma concentration of radioactivity declined biophysically with half-lives of 0.76 h (a phase) and 10.32 h (/ phase). After oral administration of 14C miconazole at a dose of 1, 3, or 10 mg/kg to male rats, the plasma concentration of radioactivity reached the maximum level within 1.25 h, after dosing and the decline of radioactivity after the maximum level was similar to that after intravenous administration. At a dose of 30 mg/kg, the pharmacokinetic profile of radioactivity in the plasma was different from that at the lower doses. In the female rats, the plasma concentration of radioactivity declined more slowly than that in male rats. The tests were conducted on pregnant rats, lactating rats, bile-duct cumulated male rats. Enterohepatic circulation was observed. In the in situ experiment, 14C miconazole injected was observed from the duodenum, jejunum, and/or ileum, but not from the stomach. 

Yoshimura et al. [132] studied the pharmacokinetics of primaquine in calves of 180—300 kg live weight. The drug was injected at 0.29 mg/kg (0.51 mg/kg as primaquine diphosphate) intravenously or subcutaneously and the plasma concentrations of primaquine and its metabolite carboxyprimaquine were determined by high performance liquid chromatography. The extrapolated concentration of primaquine at zero time after the intravenous administration was 0.5 0.48 pg/mL which decreased with an elimination half-life of 0.16 0.07 h. Primaquine was rapidly converted to carboxyprimaquine after either route of administration. The peak concentration of carboxyprimaquine was 0.5 0.08 pg/mL at 1.67 0.15 h after intravenous administration. The corresponding value was 0.47 0.07 pg/mL at 5.05 1.2 h after subcutaneous administration. The elimination half-lives of carboxyprimaquine after intravenous and subcutaneous administration were 15.06 0.99 h and 12.26 3.6 h, respectively. 

Giri, S.N., H.R. Parker, W.L. Spangler, H.P. Misra, G. Ishizaki, M.J. Schiedt, and D.B. Chandler. 1982. Pharmacokinetics of [14C]-paraquat and associated biochemical and pathologic changes in beagle dogs following intravenous administration. Fundam. Appl. Toxicol. 2 261-269. 

Yonemitsu, K. 1986. Pharmacokinetic profile of paraquat following intravenous administration to the rabbit. Foren. Sci. Int. 32 33-42. 

Generating valid in silico models requires high quality databases for model training. True values of VD in human require that the parameters are calculated from pharmacokinetic data measured after intravenous administration. From equation 7 above, calculation of VDSS requires that the dose that enters the bloodstream is known, which can only be guaranteed by intravenous... 

Jendbro M, Johansson C-J, Strandberg P, Falk-Nilsson H, Edsbacker S (2001) Pharmacokinetics of budesonide and its major ester metabolite after inhalation and intravenous administration of budesonide in the rat. Drug Metab Dispos 29 769-776. 

A series of branched aliphatic amides were prepared to evaluate the role of amide hydrolysis on the pharmacokinetics and anticonvulsant activity of valpromide analogues. Table 4.1 summarizes the structures investigated, the fraction of amide hydrolyzed (/m), and the stability in blood. These results were obtained after intravenous administration to dogs [6], The structures are classified here in order of decreasing fm. 

Aellig WH, Nuesch E. (1977). Comparative pharmacokinetic investigations with tritium-labeled ergot alkaloids after oral and intravenous administration in man. IntJ Clin Pharmacol Biopharmacy. 15(3) 106-12. 

Ding GH, Naora K, Hayashibara M, Katagiri Y, Kano Y, Iwamoto K. (1991). Pharmacokinetics of [6]-gingerol after intravenous administration in rats. Chem Pharm Bull (Tokyo). 39(6) 1612-14. Dziedzicka-Wasylewska M, Willner P, Papp M. (1997). Changes in dopamine receptor mRNA expression following chronic mild stress and chronic antidepressant treatment. Behav Pharmacol. 8(6-7) 607-18. 

Much remains to be done to improve the physicochemical properties and the pharmacokinetic characteristics of the estabhshed compound classes. A critical observer cannot help but wonder about the PK/PD profiles of many of the compoimds currently undergoing chnical development with hmited oral bioavailability, often necessitating intravenous administration, and rather short half fives in combination with often transient acetylation effects, the need for HDAC inhibitors with a more beneficial pharmacokinetic profile seems key. 

Zara G.P., Intravenous administration to rahhits of non-stealth and stealth doxorubicin loaded sohd hpid nanoparticles at increasing concentrations of stealth agent pharmacokinetics and distrihution of doxoruhicin in hrain and other tissues, J. Drug Targeting, 10, 327, 2002. 

Imipenem-cilastatin is only available for intramuscular or intravenous administration because oral bioavailability is poor. The enzyme, dehydropeptidase 1, present in renal tubules, converts imipenem to an inactive metabolite. To decrease metabolic clearance, imipenem is combined with cilastatin, an inhibitor of dehydropeptidase I. Additional pharmacokinetic information appears in Table 45.2. 

Mojaverian P., E. Radwanski, M.B. Affrime, M.N. Cayen, and C.C. Lin (1994). Pharmacokinetics of the triazole antifungal agent genaconazole in healthy men after oral and intravenous administration. Antimicrobial Agents and Chemotherapy 38 2758-2762. 

Stass H. and D. Kubitza (1999). Pharmacokinetics and elimination of moxifloxacin after oral and intravenous administration in man. Journal of Antimicrobial Chemotherapy 43(Suppl. B) 83-90. 

Jansen, J.A., J. Andersen, and J.S. Schou. 1984. Boric acid single dose pharmacokinetics after intravenous administration to man. Arch. Toxicol. 55 64-67. 

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