Large Theophylline Requirements due to High Theophylline Clearance: Verification by the Antipyrine Test

Blyden, Gershwin T.; LeDuc, Barbara W.; Greenblatt, David J.

doi:10.1159/000138173

Cited by 11 publications

(3 citation statements)

References 13 publications

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“…In urine, concentrations of intact antipyrine and its 3 principal metabolites (4-hydroxyantipyrine, norantipyrine. and 3-hydroxy methyl antipyrine) were also quantitated by high pres sure liquid chromatography [Blyden et al, 1986], Both assays have senstivity limits of approximately 1.0 pg/ml or better.…”

Section: Antipyrine Studymentioning

confidence: 99%

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

et al. 1990

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The effect of cigarette smoking on drug oxidation and conjugation was studied using antipyrine and acetaminophen as marker compounds. For the antipyrine study, healthy cigarette smokers (n = 30) and nonsmoking controls (n = 53) received a single 1.0-gram intravenous dose of antipyrine. For the acetaminophen study, 14 smokers and 15 nonsmokers received a 650-mg intravenous dose of acetaminophen. The clearance of antipyrine was significantly increased (0.93 vs. 0.60 ml/min/kg, p < 0.0001) and elimination half-life was correspondingly reduced (8.9 vs. 13.0 h, p < 0.0001) in smokers compared to nonsmoking controls. Total recovery of antipyrine and metabolites excreted in urine did not differ between groups, but there was a significantly increased fractional clearance of antipyrine via formation of 4-hydroxyantipyrine and 3-hydroxymethyl metabolites in smokers. Fractional clearance via formation of norantipyrine did not differ significantly between groups. Comparison of acetaminophen kinetics between smokers and nonsmokers indicated no significant differences in elimination half-life, clearance or volume of distribution. Thus, cigarette smoking is more likely to induce drug oxidation rather than drug conjugation. However, not all oxidative pathways are equally influenced; induction effects of smoking are highly substrate selective and pathway specific.

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Section: Antipyrine Studymentioning

confidence: 99%

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

et al. 1990

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“…Concentrations of intact antipyrine and its three principal metabolites (norantipyrine, 4-hydroxyantipyrine and 3-hydroxymethyl antipyrine) in all urine samples were also determined by HPLC (Blyden et al 1986). Plasma lorazepam (Greenblatt et al 1978) and alprazolam concentrations were analysed by electron-capture gas-liquid chromatography.…”

Section: Analysis Of Samplesmentioning

confidence: 99%

Lack of Effect of Influenza Vaccine on the Pharmacokinetics of Antipyrine, Alprazolam, Paracetamol (Acetaminophen) and Lorazepam

Scavone

Blyden

Greenblatt

1989

Clinical Pharmacokinetics

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31 healthy male (n = 17) and female (n = 14) volunteers, aged 20 to 45 years, were divided into 4 groups and received on 3 separate occasions either: paracetamol (acetaminophen) 650mg intravenously (n = 9); alprazolam 1mg orally (n = 7); antipyrine (phenazone) 1g intravenously (n = 8); or lorazepam 2mg intravenously (n = 7). Doses were administered prior to influenza vaccine (0.5ml, intramuscularly) and at 7 and 21 days post-vaccination. The overall differences among the 3 trials in clearance of antipyrine were of borderline significance (p less than 0.0611), with a trend towards reduced clearance in both of the post-vaccination trials. There were no overall differences observed in the elimination half-life of antipyrine, nor were there significant differences between trials in cumulative urinary excretion or fractional recovery of intact antipyrine, 4-hydroxyantipyrine, norantipyrine, or 3-hydroxymethyl antipyrine. For paracetamol and alprazolam, there were no significant differences among the 3 trials in any of the kinetic variables. The elimination half-life of lorazepam varied significantly among trials, but differences were small and not systematic. Lorazepam clearance did not vary significantly among trials. Thus, clearance of drugs which undergo hepatic conjugative reactions such as glucuronidation and sulphation are unlikely to be affected by the coadministration of influenza vaccine. Furthermore, not all drugs which are biotransformed by hepatic microsomal oxidation necessarily have impaired clearance due to coadministration of influenza vaccine.

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“…After hydrolysis with ,-glucuronidase and sulfatase (Glusulase; DuPont Biomedical, Boston, Mass. ), the concentrations of antipyrine and its three major metabolites (HMA, OHA, and NORA) in urine were determined by HPLC by previously described procedures (6).…”

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confidence: 99%

Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism

Borcherding

Bastian

Self

et al. 1992

Antimicrob Agents Chemother

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The effects of two short-term chemoprophylaxis regimens of rifampin (2 or 4 days) on oxidative metabolism were investigated in 14 healthy subjects. Seven subjects received 600 mg of rifampin twice daily on study days 6 and 7 (group A), and seven subjects received 600 mg of rifampin once daily on days 4, 5, 6, and 7 (group B). Antipyrine (18 mg/kg of body weight) was administered orally on days 1, 8, and 15. Short-term rifampin regimens increased oral clearance of antipyrine in both groups compared with the baseline value (P less than 0.05), and group B displayed a larger percent increase over the baseline value than group A did (70.5 +/- 14.3 versus 33.1 +/- 18.1; P less than 0.05). The partial metabolic clearance (CLM) of antipyrine to 3-hydroxymethylantipyrine (HMA) on day 8 increased 71 and 108% for regimens A and B, respectively (P less than 0.05 for both). The corresponding increases in CLM to norantipyrine (NORA) were 57 and 98% (P less than 0.05 for both). CLM to 4-hydroxyantipyrine (OHA) on day 8 increased 64% for regimen A (P = 0.08) and 97% for regimen B (P less than 0.05) compared with the baseline. Although CLM to HMA and OHA on day 15 remained greater than 50% over the baseline with both regimens, CLM to NORA on day 15 was less than 25% over the baseline with both regimens. Thus, both short-term rifampin chemoprophylaxis regimens increased antipyrine clearance for at least 1 week. The increase tended to be higher with the 4-day regimen. The pattern observed for the CLMS suggests that more than one P-450 enzyme is affected.

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Large Theophylline Requirements due to High Theophylline Clearance: Verification by the Antipyrine Test

Cited by 11 publications

References 13 publications

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

Differential Effect of Cigarette Smoking on Antipyrine Oxidation versus Acetaminophen Conjugation

Lack of Effect of Influenza Vaccine on the Pharmacokinetics of Antipyrine, Alprazolam, Paracetamol (Acetaminophen) and Lorazepam

Two- and four-day rifampin chemoprophylaxis regimens induce oxidative metabolism

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