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British Journal of Clinical Pharmacology Jun 1987Antipyrine half-life has been determined from measurements of antipyrine concentrations in spontaneously voided urine specimens in eleven subjects, studied on a total of...
Antipyrine half-life has been determined from measurements of antipyrine concentrations in spontaneously voided urine specimens in eleven subjects, studied on a total of forty-seven different occasions while receiving no drugs, interferon or ketoconazole. Plasma and saliva half-lives show good intrasubject correlation. Plasma and urine half-lives show good intrasubject correlation provided total urine output is at least 1.1 l day-1. The range of intrasubject correlation coefficients for plasma and urinary half-lives was 0.76 to 0.98, with a median value of 0.85. Saliva and urine half-lives show good intrasubject correlation, with the range of intrasubject correlation coefficients from 0.74 to 0.98, and with a median value of 0.75. There is a small but consistent bias towards shorter urinary half-life estimates; this averaged 0.75 h for the plasma-urine studies and 0.192 h for the saliva-urine studies. There were parallel changes in antipyrine half-life estimated from plasma and urine for one of our subjects who received multiple doses of recombinant beta-interferon and had a 150% increase in antipyrine half-life over the study period.
Topics: Adult; Aged; Antipyrine; Female; Half-Life; Humans; Interferons; Ketoconazole; Male; Middle Aged; Saliva
PubMed: 2440468
DOI: 10.1111/j.1365-2125.1987.tb03106.x -
The Journal of Pharmacy and Pharmacology Mar 1982A t.l.c.-assay has been developed for the simultaneous determination from the urine of man and animals of three major hydroxylated metabolites of antipyrine... (Comparative Study)
Comparative Study
A t.l.c.-assay has been developed for the simultaneous determination from the urine of man and animals of three major hydroxylated metabolites of antipyrine (4,4'-dihydroxy-antipyrine, 4-hydroxy-antipyrine, 3-hydroxymethyl-antipyrine). The methodology is also applicable to bile fluid, liver perfusate and liver homogenate. Genuine conjugates are cleaved by acid hydrolysis and free, acid stable metabolites are extracted. Extracts are subjected to t.l.c. and the chromatograms analysed quantitatively by u.v.-reflectance measurements using authentic materials as standards. Calibration curves are linear with a correlation coefficient r greater than 0.990. Recovery for each metabolite is greater than 95%. Reproducibility of the method is good, with variation coefficients in the range of 3-7%, depending on concentration. The sensitivity of the method is sufficient for practical needs. The specificity of the procedure was confirmed using radio-labelled antipyrine. In man, 4-hydroxy-antipyrine is the principal hydroxylation product in this series, accounting for about 35-40% of the dose. 3-Hydroxymethyl-antipyrine makes up for about 13-17% and 4,4'-dihydroxy-antipyrine represents 3-6% of the dose of antipyrine. In the rat, 4-hydroxy-antipyrine accounts for about 15-31%, 3-hydroxymethyl-antipyrine for 22-28% and 4,4'-dihydroxy-antipyrine for up to 11-18% of the dose. Variation of this pattern in different strains is moderate. In both species, the major portion of phase-I metabolites is excreted as conjugates. Part of them appears in a free form.
Topics: Adult; Animals; Antipyrine; Biotransformation; Chromatography, Thin Layer; Drug Stability; Glucuronates; Humans; Hydroxylation; Kinetics; Male; Rats; Rats, Inbred Strains
PubMed: 6121894
DOI: 10.1111/j.2042-7158.1982.tb04215.x -
Clinical Pharmacology and Therapeutics Sep 1982Antipyrine clearance (Cl(AP)) is widely used for assessment of microsomal liver function. The usual procedure involves collection of 4 to 7 samples of plasma or saliva...
Antipyrine clearance (Cl(AP)) is widely used for assessment of microsomal liver function. The usual procedure involves collection of 4 to 7 samples of plasma or saliva obtained during 24 to 48 hr. To determine whether this procedure could be simplified it was compared with one based on a single sample (sCl(AP)) and an estimated volume of distribution (V(D)) in 142 persons. VD was estimated from body weight, in kilograms (BW), height, in centimeters (BH), age in years, and sex, or assumed to be 40 l. The agreement between values of Cl(AP and sCl(AP) increased with the time of the single sample and the two clearance estimates were nearly identical in all cases when the sample was taken after 18 hr. The method used for assessment of V(D) had only a small influence on the agreement. It is suggested that antipyrine clearance (in ml/min) is estimated as (formula: see text) where D is the dose of antipyrine (in mg), c(t) the concentration of antipyrine (in mg/t) at sampling time t (in min), t should be about 1440 min (24hr), and V(D) (in l) is calculated as 0.2363 X BW + 0.1962 X BH - 0.0272 X age - 10.26 (women) or 0.3625 X BW + 0.2239 X BH - 0.1387 X age - 14.47 (men). Little information is lost, however, if a fixed volume of 40 l is used. Then, if the dose is l gm, c(t) is expressed in milligrams per liter, and the sampling time is 24 hr, sCl(AP) = (3.28 - ln c(t)) X 28 ml/min.
Topics: Adult; Antipyrine; Female; Humans; Kinetics; Male; Microsomes, Liver; Middle Aged; Regression Analysis; Saliva
PubMed: 7105629
DOI: 10.1038/clpt.1982.177 -
Drug Metabolism and Disposition: the... 1981The rates of antipyrine and hexobarbital elimination from blood or plasma were used to determine whether the antibiotic rifampicin is an inducer of microsomal oxidative...
The rates of antipyrine and hexobarbital elimination from blood or plasma were used to determine whether the antibiotic rifampicin is an inducer of microsomal oxidative drug metabolism in the pig. Treatment with rifampicin (300 mg, po, twice daily for 7 days) decreased hexobarbital and antipyrine elimination half-lives by 65 and 62%, respectively. This was associated with an increase of the metabolic clearance by 222% for hexobarbital and 255% for antipyrine. However, not in all pigs was an increase of antipyrine clearance observed. The antipyrine metabolite profile was determined before and after rifampicin treatment. The partial clearance of 4-hydroxyantipyrine, as measured on the basis of urinary excretion data, increased about fourfold. Neither norantipyrine nor 3-hydroxymethylantipyrine were detectable in urine before rifampicin treatment. Only after rifampicin treatment could a small amount of 3-hydroxymethylantipyrine be measured. It is concluded that rifampicin is a potent inducer of microsomal oxidative drug metabolism in the pig. In contrast to other animal species, the pig seems to represent a suitable animal model for further study of rifampicin induction. Because of the increase of hexobarbital clearance in all cases and lack of increase of antipyrine clearance in some pigs, a similarity between the situation in man and pig seems to exist.
Topics: Animals; Antipyrine; Half-Life; Hexobarbital; Male; Microsomes; Oxidation-Reduction; Rifampin; Swine
PubMed: 6120813
DOI: No ID Found -
Clinical Pharmacology and Therapeutics Aug 1993Antipyrine half-life determined on three to five separate occasions over a period ranging from 3 weeks to 1 year was highly reproducible in each of 20 elderly subjects...
Antipyrine half-life determined on three to five separate occasions over a period ranging from 3 weeks to 1 year was highly reproducible in each of 20 elderly subjects (12 women and 8 men; mean age, 83 years). The mean within-subject coefficient of variation for antipyrine half-life was 9.6%, whereas the between-subject coefficient of variation was 33.3%. These findings indicate high reproducibility of individual rates of drug metabolism in medically stable elderly subjects.
Topics: Aged; Aged, 80 and over; Antipyrine; Female; Half-Life; Humans; Male; Reproducibility of Results
PubMed: 8354024
DOI: 10.1038/clpt.1993.126 -
The Journal of Pharmacology and... Feb 1992We examined the in vivo absorption and pharmacokinetics of antipyrine, a base that is unionized at physiologic pH, from the urinary bladder of adult female Fischer rats....
We examined the in vivo absorption and pharmacokinetics of antipyrine, a base that is unionized at physiologic pH, from the urinary bladder of adult female Fischer rats. The clearance of an i.v. dose of antipyrine (25 mg/kg) was found to vary considerably between animals, which is consistent with the literature data. Therefore, it was necessary to simultaneously determine drug clearance and bladder absorption in the same animal. This was accomplished by giving concomitantly an i.v. dose of [14C]antipyrine (2.5 muCi, about 90 micrograms/kg) via a jugular vein catheter and an intravesical dose of unlabeled antipyrine (33 mg/kg) via a urethral catheter. Unlabeled antipyrine was detected in plasma, indicating the absorption of antipyrine into systemic circulation. The bioavailability of the intravesical dose was calculated using the clearance of [14C]antipyrine and the plasma concentrations of unlabeled antipyrine. The intravesical dose was withdrawn through the urethral catheter after 90 min. To minimize mechanical manipulation and damage, the bladder was not rinsed. This may have caused the incomplete recovery of the unabsorbed dose; about 65 +/- 18% (mean +/- S.D.) of the dose was recovered at 90 min. Maximal plasma concentrations were achieved at 10 to 48 min after removal of the intravesical dose, which is consistent with a continued absorption of the residual dose. The intravesical bioavailability was variable between animals, with an average of 11.6 +/- 6.4% (mean +/- S.D.; range, 4.1-19.2%). In conclusion, these data demonstrate that neutral drugs such as antipyrine are absorbed from the bladder, that the extent of absorption is variable and that the urinary bladder may be a site of significant re-entry of drugs into the systemic circulation.
Topics: Animals; Antipyrine; Biological Availability; Chromatography, High Pressure Liquid; Female; Kinetics; Rats; Rats, Inbred F344; Urinary Bladder
PubMed: 1738110
DOI: No ID Found -
Journal of Pharmacological and... Nov 1992The well-controlled microdialysis (MD) study of substance permeation into brain extracellular fluid (ECF) and cerebrospinal fluid requires consideration of blood-brain...
The well-controlled microdialysis (MD) study of substance permeation into brain extracellular fluid (ECF) and cerebrospinal fluid requires consideration of blood-brain barrier (BBB) integrity, which might be compromised by microdialysis probe implantation. Others have assessed BBB integrity with radionuclide markers. A nonradionuclide marker may be desirable in many studies. A charged antipyrine analogue may be useful to determine BBB integrity with concomitant antipyrine characterization of probe efficiency (Yokel et al., 1992, J Pharmacol Toxicol Methods 27:135-142), and may not require another analytical technique. We synthesized, validated, and evaluated 4-trimethylammonium antipyrine (4TMA-AP) as a BBB integrity marker. BBB permeation was determined by calculation of a BBB integrity percentage (Pi) from brain/blood concentrations. The PiS of Evan's blue, which does not permeate the intact BBB, and 4TMA-AP were not significantly different in rats without known BBB disruption, suggesting a lack of 4TMA-AP permeation through the intact BBB. When MD probes were slowly implanted into the frontal cortex, 4TMA-AP PiS were usually zero. Intracarotid oleic acid injection to open the BBB significantly increased 4TMA-AP PiS, suggesting that 4TMA-AP entered brain ECF when the BBB was compromised. Rapid probe implantation produced increased 4TMA-AP PiS, suggesting BBB disruption. The predicted appearance of 4TMA-AP in brain ECF suggests that it is a BBB integrity marker.
Topics: Animals; Antipyrine; Blood-Brain Barrier; Brain; Chromatography, High Pressure Liquid; Dialysis; Evans Blue; Male; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley
PubMed: 1489983
DOI: 10.1016/1056-8719(92)90074-b -
British Journal of Clinical Pharmacology Dec 1979The plasma elimination rate of antipyrine, as measured by the salivary concentration decay, and the urinary excretion of antipyrine and its primary metabolites... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The plasma elimination rate of antipyrine, as measured by the salivary concentration decay, and the urinary excretion of antipyrine and its primary metabolites 4-hydroxy-antipyrine, norantipyrine, 3-hydroxymethyl-antipyrine and 3-carboxy-antipyrine was studied in five healthy volunteers, who received 250, 500 and 1000 mg antipyrine orally in a cross-over design. The mean antipyrine half-life and metabolic clearance were 11.5 ± 2.5 h (range 10.2-16.9 h) and 3.4 ± 0.9 l/h (range 1.7-4.2 l/h) respectively after 500 mg. These values were not significantly different after 250 or 1000 mg ( > 0.1; paired -test). In 52 h urine 3.3 ± 1.2% of the dose of 500 mg antipyrine was excreted unchanged as antipyrine, 28.5 ± 2.2% as 4-hydroxy-antipyrine, 16.5 ± 6.0% as norantipyrine, 35.1 ± 7.2% as 3-hydroxymethyl-antipyrine and 3.3 ± 0.8% as 3-carboxy-antipyrine. The values obtained at the other dose levels were not significantly different ( > 0.1; paired -test). At all dose levels 4-hydroxy-antipyrine and norantipyrine were excreted in urine entirely as glucuronides. After 500 mg antipyrine, 3-hydroxymethyl-antipyrine was excreted as glucuronide to the extent of 58 ± 9% of the total excreted amount. This percentage was not significantly different at the other dose levels. 3-Carboxy-antipyrine was excreted in the free form at all three dose levels. From 12 h of drug intake onwards, the urinary excretion rate curves of antipyrine and all its metabolites declined mono-exponentially with about the same half-life as the parent compound in saliva. The half-lives calculated from the excretion rate curves of 4-hydroxy-antipyrine, norantipyrine and 3-hydroxymethyl-antipyrine correlated significantly with the half-life of antipyrine in plasma. At all dose levels a relative delay in urinary excretion of 3-hydroxymethyl-antipyrine was observed compared to the urinary excretion of antipyrine and the other metabolites. The ratios of the cumulative amounts of metabolites excreted in 24 h, were essentially the same as those measured in the 52 h samples.
Topics: Administration, Oral; Antipyrine; Biotransformation; Half-Life; Humans; Male; Time Factors
PubMed: 533575
DOI: 10.1111/j.1365-2125.1979.tb01040.x -
Liver Aug 1985We investigated antipyrine clearance and urinary excretion of 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and nor-antipyrine in rats after 70% partial hepatectomy....
We investigated antipyrine clearance and urinary excretion of 4-hydroxyantipyrine, 3-hydroxymethylantipyrine and nor-antipyrine in rats after 70% partial hepatectomy. Antipyrine clearance recovered more slowly than liver weight but after 240 h both liver weight and antipyrine clearance had reached control values. During hepatic regeneration conversion of antipyrine to the three major metabolites was reduced, conversion to 3-hydroxymethylantipyrine being reduced more than conversion to the other metabolites. Antipyrine clearance was closely correlated to liver weight (r = 0.81), indicating a close relation between the functional hepatic mass and the liver weight during hepatic regeneration.
Topics: Animals; Antipyrine; Edaravone; Female; Liver Diseases; Liver Regeneration; Organ Size; Rats; Rats, Inbred Strains; Time Factors
PubMed: 4058271
DOI: 10.1111/j.1600-0676.1985.tb00237.x -
Spectrochimica Acta. Part A, Molecular... Nov 2012In this work, 4-(2-fluorobenzylideneamino)antipyrine (FBIAAP) was synthesized and characterized by elemental analysis, XRD, FT-IR, FT-Raman and UV-Vis techniques as well...
In this work, 4-(2-fluorobenzylideneamino)antipyrine (FBIAAP) was synthesized and characterized by elemental analysis, XRD, FT-IR, FT-Raman and UV-Vis techniques as well as density functional calculations. The studied molecule adopts a trans configuration about the imine CN bond, and adjacent molecules are linked through two kinds of weak hydrogen bonds to form supramolecular layered structures along the ab plane. Vibrational spectral analyses show that the benzene moiety directly attached to the central pyrazoline shows good vibrational isolation from the other moiety of pyrazole-imino-benzene presenting good vibrational resonances. UV-vis absorption bands mainly belong to n→π and π→π according to the electron transfer orbital assignments for the electron absorption spectrum of FBIAAP. The first-order hyperpolarizability of FBIAAP is 44.9 times that of urea theoretically. In addition, the thermodynamic properties were also obtained theoretically from the harmonic frequencies of the optimized structure.
Topics: Antipyrine; Crystallography, X-Ray; Hydrogen Bonding; Light; Models, Molecular; Molecular Conformation; Nonlinear Dynamics; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Thermodynamics; Vibration
PubMed: 22925977
DOI: 10.1016/j.saa.2012.07.117