Drugs online research references
Eur J Clin Pharmacol. 1982;22(1):77-84.
Kinetics of allopurinol after single intravenous and oral doses. Noninteraction with benzbromarone and hydrochlorothiazide.
Breithaupt B, Tittel M.
An high-pressure liquid chromatographic method was used to measure allopurinol and oxipurinol in plasma and urine in 6 healthy volunteers after a single intravenous or oral dose of allopurinol. The influence of coadministered benzbromarone and hydrochlorothiazide on the pharmacokinetics of allopurinol and oxipurinol was also investigated. After intravenous injection of allopurinol 300 mg the plasma disappearance was biexponential, with a mean distribution half-life of 2.32 +/- 1.08 min (mean +/- SD) and an elimination half-life of 47.8 +/- 10.6 min. The total clearance of allopurinol was 11.37 +/- 2.70 ml/min/kg, whereas its renal clearance was only 1.73 +/- 0.79 ml/min/kg. Oxipurinol disappeared monoexponentially from plasma with a mean half-life of 12.2 +/- 2.6 h. Its renal clearance was 0.42 +/- 0.091 ml/min/kg. After oral administration of allopurinol 300 mg the peak plasma concentration of 2.1 +/- 0.6 micrograms/ml (1.5 x 10(-5) M) was reached within 30 to 120 min. The peak level of oxipurinol of 5.8 +/- 1.5 micrograms/ml (3.8 x 10(-5) M) was found within 2 to 5 h after intravenous and oral allopurinol. The bioavailability of oral allopurinol computed from plasma data was 90.4 +/- 8.7%. The total recovery from urine was 77% (allopurinol 8%, oxipurinol 69%) after oral and 88% after i.v. administration. It was concluded that about 10% of the oral dose was not absorbed and that 12% was eliminated by an unknown mechanism, presumably as riboside. The pharmacokinetics of allopurinol and oxipurinol were not significantly influenced by coadministration of benzbromarone or hydrochlorothiazide.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7094977&dopt=Abstract
uclink4.berkeley.edu
Oxidative DNA damage is important in aging and the degenerative diseases of aging such as cancer. Estimates commonly rely on measurements of 8-oxo-2'-deoxyguanosine (oxo8dG), an adduct that occurs in DNA and is also excreted in urine after DNA repair. Here we examine difficulties inherent in the analysis of oxo8dG, identify sources of artifacts, and provide solutions to some of the common methodological problems. A frequent criticism has been that phenol in DNA extraction solutions artificially increases the measured level of oxo8dG. We found that phenol extraction of DNA contributes a real but minor increase in the level of oxo8dG when compared, under equivalent conditions, with a successful nonphenol method. A more significant reduction in the baseline level was achieved with a modification of the recently introduced chaotropic NaI method, reducing our estimate of the level of steady-state oxidative adducts by an order of magnitude to 24,000 adducts per cell in young rats and 66,000 adducts per cell in old rats. Of several alternative methods tested, the use of this chaotropic technique of DNA isolation by using NaI produced the lowest and least variable oxo8dG values. In further studies we show that human urinary 8-oxo-guanine (oxo8Gua) excretion is not affected by the administration of allopurinol, suggesting that, unlike some methylated adducts, oxo8Gua is not derived enzymatically from xanthine oxidase. Lastly, we discuss remaining uncertainties inherent both in steady-state oxo8dG measurements and in estimates of endogenous oxidation ("hit rates") based on urinary excretion of oxo8dG and oxo8Gua.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9419368&dopt=Abstract
Am J Physiol. 1989 Jul;257(1 Pt 2):R237-45.
Allopurinol kinetics in humans as a means to assess liver function: design of a loading test.
Van Waeg G, Groth T.
Department of Clinical Chemistry, Uppsala University, Sweden.
A six-compartment model of allopurinol and oxipurinol kinetics, after intravenous allopurinol injection in the human, is studied further to improve the blood and urine specimen collection schedule for clinical use. The effects of various error sources are also investigated by simple techniques like real data set truncation and adding normally distributed random errors to data obtained from simulation of allopurinol and oxipurinol plasma curves with preset parameters. All parameters estimation is performed with the NONLIN parameter estimation program. Main interest was focused on estimation of the fractional rate constant of transport from the central "extracellular" compartment to the metabolically active compartment. This parameter is regarded as a lumped measure of liver perfusion and liver cell membrane transport. The blood sampling schedule can be reduced to six specimens collected over 60 min, without affecting the accuracy and precision of estimated clinical parameters. The maximum allowable coefficient of variation for preanalytical errors and the analytical within-run and between-run errors are around 5, 4, and 5%, respectively. Analytical between-run bias up to 20% does not affect the estimate of the principal parameter, when both allopurinol and oxipurinol are biased in the same direction. Collection and analysis of urine samples was shown to be unnecessary.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2750963&dopt=Abstract
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