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1. |
Should hematopoietic growth factors routinely be given concurrently with cytotoxic chemotherapy? |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 1-6
Alexandra J. Croockewit,
Peter P. Koopmans,
Ben E. Pauw,
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摘要:
Clinical Pharmacology&Therapeutics(1996)59, 1–6; do
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90016-8
年代:1996
数据来源: WILEY
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2. |
Statement of announcement |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 6-6
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摘要:
Clinical Pharmacology&Therapeutics(1996)59, 6–6; do
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90017-X
年代:1996
数据来源: WILEY
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3. |
Rifampin drastically reduces plasma concentrations and effects of oral midazolam |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 7-13
Janne T. Backman,
Klaus T. Olkkola,
Pertti J. Neuvonen,
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摘要:
BackgroundMidazolam is a short‐acting benzodiazepine that is metabolized by CYP3A enzymes. Rifampin is a potent enzyme inducer that may seriously interact with some substrates of CYP3A4.MethodsThe possible interaction between rifampin and midazolam was investigated in a double‐blind, randomized crossover study of two phases. Rifampin (600 mg once daily) or placebo was administered to 10 healthy subjects for 5 days. On the sixth day, the subjects were given 15 mg oral midazolam. Plasma samples were collected for determination of midazolam, and pharmacodynamic effects were measured for 10 hours.ResultsRifampin pretreatment decreased the area under the plasma midazolam concentration‐time curve by 96% (i.e., from 10.2 ± 0.8 to 0.42 ± 0.05 μg · min/ml [mean ± SEM;p<0.001]) and the maximum concentration by 94% (i.e., from 55 ± 4 to 3.5 ± 0.7 ng/ml [p<0.001]). The elimination half‐life of midazolam was decreased from 3.1 ± 0.2 to 1.3 ± 0.2 hours by rifampin (p<0.001). During the rifampin phase, the pharmacodynamic effects of midazolam were markedly smaller than the effects during the placebo phase in all the tests (e.g., the Digit Symbol Substitution Test;p<0.001).ConclusionsThe observed substantial decrease in plasma concentrations and effects of midazolam most likely results from induction of CYP3A4 by rifampin in both the gut wall and the liver. Orally administered midazolam is ineffective during rifampin treatment.Clinical Pharmacology&Therapeutics(19
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90018-1
年代:1996
数据来源: WILEY
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4. |
Atovaquone inhibits the glucuronidation and increases the plasma concentrations of zidovudine |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 14-21
Belle L. Lee,
Martin G. Täuber,
Brian Sadler,
Donna Goldstein,
Henry F. Chambers,
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摘要:
The pharmacokinetic interaction between atovaquone, a 1,4‐hydroxynaphthoquinone, and zidovudine was examined in an open, randomized, three‐phase crossover study in 14 patients infected with human immunodeficiency virus. Atovaquone (750 mg every 12 hours) and zidovudine (200 mg every 8 hours) were given orally alone and in combination. Atovaquone significantly increased the area under the zidovudine concentration‐time curve (AUC) (1.82 ± 0.62 μg · hr/ml versus 2.39 ± 0.68 μg · hr/ml;p<0.05) and decreased the oral clearance of zidovudine (2029 ± 666 ml/min versus 1512 ± 464 ml/min;p<0.05). In contrast, atovaquone tended to decrease the AUC of zidovudine‐glucuronide (7.31 ± 1.51 μg · hr/ml versus 6.89 ± 1.42 μg · hr/ml;p<0.1) and significantly decreased the ratio of AUC zidovudine‐glucuronide/AUC zidovudine (4.48 ± 1.94 versus 3.12 ± 1.1;p<0.05). The maximum concentration of zidovudine‐glucuronide was significantly lowered by atovaquone (5.7 ± 1.5 versus 4.57 ± 0.97 μg/ml;p<0.05). Zidovudine had no effect on the pharmacokinetic disposition of atovaquone. Atovaquone appears to increase the AUC of zidovudine by inhibiting the glucuronidation of zidovudine.Clinical Pharmacology&Th
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90019-3
年代:1996
数据来源: WILEY
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5. |
Inhibition of dihydropyrimidine dehydrogenase by 5‐propynyluracil, a metabolite of the anti‐varicella zoster virus agent netivudine |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 22-31
Richard Peck,
Rebecca Wiggs,
Julia Callaghan,
Ray Wootton,
Peter Crome,
Ian Fraser,
Lloyd Frick,
John Posner,
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摘要:
ObjectiveTo study the effects of the anti‐herpetic drug netivudine on dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them to concentrations of netivudine and its metabolite 5‐propynyluracil.MethodsThree groups of eight elderly volunteers received 400 or 800 mg netivudine or placebo once daily for 8 days. Plasma netivudine, 5‐propynyluracil, and uracil, an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed before the first dose and on days 2, 3, 5, 7, and 8. Full plasma profiles of netivudine and 5‐propynyluracil were determined after the last dose.ResultsPlasma uracil was unquantifiable in all subjects before the first dose and at all time points in the placebo group. In recipients of netivudine it reached a plateau between days 3 and 5, with mean values of 23.2 and 23.5 μmol/L on day 8 in the subjects who received 400 and 800 mg. Plasma netivudine concentrations were approximately dose proportional, but 5‐propynyluracil concentrations were similar in both groups. The half‐maximal rise in plasma uracil occurred after a cumulative 5‐propynyluracil exposure of 120 μmol/L · hr; such exposures will be achieved even after doses as low as 50 to 100 mg daily.ConclusionsNetivudine dosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase. Coadministration with the antimetabolite 5‐fluorouracil will require a substantial reduction in 5‐fluorouracil dose to avoid toxicity but may also improve the therapeutic index of 5‐fluorouracil.Clinical Pharmacology&Therapeuti
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90020-X
年代:1996
数据来源: WILEY
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6. |
Pharmacokinetics of vinorelbine in patients with liver metastases |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 32-40
Isabelle Robieux,
Roberto Sorio,
Eugenio Borsatti,
Renato Cannizzaro,
Vinicio Vitali,
Paola Aita,
Andrea Freschi,
Enzo Galligioni,
Silvio Monfardini,
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摘要:
BackgroundThe main elimination pathway of vinorelibine is hepatic metabolism, and the clearance of vinorelbine could be reduced in patients with liver metastases.ObjectivesTo study the pharmacokinetics of vinorelbine in patients who have advanced breast cancer with or without liver metastases and to study the relationship between hepatic function and vinorelbine clearance.Patients and MethodsWe studied 29 patients with advanced breast cancer: 19 with liver metastases and 10 control patients with extrahepatic metastases (mean age, 61 years; age range, 38 to 81 years). The vinorelbine dose was 30 mg/m2as a short intravenous infusion; the dose was reduced by 50% in patients with bilirubin>2 mg/dl. Patients were classified by ultrasonographic estimation of the liver volume replaced by tumor (%LVRT). Standard liver function tests and a monoethylglycinexylidide test (a quantitative liver function test based on lidocaine metabolite formation) were performed. Vinorelbine was assayed in plasma by HPLC with fluorescence detection. Vinorelbine determination was impossible in two patients with more than 75% LVRT because of interferences. Pharmacokinetic parameters were calculated with a noncompartimental method and compared by means of the Kruskal‐Wallis test.ResultsA lower vinorelbine clearance rate was observed in the five patients with more than 75% LVRT (22.9 L/hr/m2) compared with the 10 patients with no liver metastases (48.0 L/hr/m2) and the 12 patients with 25% to 75% LVRT (45.3 L/hr/m2). Terminal elimination half‐life and apparent volume of distribution were not significantly different among groups. The monoethylglycinexylidide test had a significant correlation with vinorelbine clearance. (r2= 0.70;p= 10−4).ConclusionsThese results support vinorelbine dose reduction in patients with severe liver failure but not in patients with moderate secondary liver involvement. The monoethylglycinexylidide test may prove to be useful for vinorelbine dose individualization.Clinical Pharmacology&Therapeutics(1996)59, 32–
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90021-1
年代:1996
数据来源: WILEY
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7. |
Decreased intestinal CYP3A in celiac disease: Reversal after successful gluten‐free diet: A potential source of interindividual variability in first‐pass drug metabolism |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 41-46
Chim C. Lang,
R. Michael Brown,
Mark T. Kinirons,
Mary‐Ann Deathridge,
F. Peter Guengerich,
Dermot Kelleher,
D. Sean O'Briain,
Fayez K. Ghishan,
Alastair J. J. Wood,
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摘要:
BackgroundCytochrome P450 (CYP) 3A is constitutively expressed in human intestinal villi and may account for significant “first‐pass” prehepatic metabolism of a number of drugs in the intestine. Celiac disease results in small intestinal atrophy. We hypothesized that this would result in a loss of CYP3A.MethodsFormalin‐fixed jejunal biopsy specimens taken from nine patients with celiac disease at variable times before and after treatment with a gluten‐free diet were immunoperoxidase stained after incubation with anti‐CYP3A4 rabbit antisera (1:2000 dilution). The amount of immunoreactive CYP3A was determined by two observers who were blinded to the treatment states of the patients. Staining intensity was graded on a numerical scale from 1 to 4+ on the basis of intensity of staining in individual enterocytes, as well as the total number of enterocytes stained.ResultsSlides of biopsy specimens from all nine untreated patients with celiac disease were graded 1. Treatment with a gluten‐free diet was associated with a significant increase in CYP3A immunoreactive protein in small bowel biopsy specimens (p<0.05, Wilcoxon signed‐rank test).ConclusionsWe conclude that patients with celiac disease have low intestinal CYP3A immunoreactivity and that treatment with a gluten‐free diet is associated with an increase in intestinal CYP3A immunoreactive protein. Our findings suggest that intestinal disease and variability in intestinal CYP3A activity might be an unexamined variable that may contribute to interindividual variability in drug disposition.Clinical Pharmacology&Therapeutics(19
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90022-3
年代:1996
数据来源: WILEY
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8. |
Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving cyclosporine |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 47-51
C. Michael Stein,
Mark T. Kinirons,
Theodore Pincus,
Grant R. Wilkinson,
Alastair J. J. Wood,
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摘要:
IntroductionCytochrome P4503A (CYP3A) is primarily responsible for the metabolism of cyclosporine and that of many other drugs. Several substrates of CYP3A have been investigated for use as pharmacologic probes to predict the CYP3A‐metabolizing capacity of an individual and, therefore, the disposition of other CYP3A substrate drugs. One such measure of CYP3A activity is the14C erythromycin breath test, which has been applied to the prediction of cyclosporine disposition. However, the test has practical limitations. Because of this, the 0‐ to‐8‐hour urinary dapsone recovery ratio has been studied as an alternative and more practical probe of CYP3A activity.MethodsThe dapsone recovery ratio and the14C erythromycin breath test were correlated with cyclosporine concentrations in 16 patients with rheumatoid arthritis to determine the usefulness of the dapsone recovery ratio as an alternative to the14C erythromycin breath test. The erythromycin breath test showed a fourfold variation between subjects and correlated weakly with trough cyclosporine concentrations (r= −0.50,P<0.05), whereas the dapsone recovery ratio varied only approximately twofold between subjects and did not correlate with trough cyclosporine concentrations (r= 0.02,p= 0.94). The correlation between the dapsone recovery ratio and the erythromycin breath test (r= 0.22,p= 0.41) was not significant.ConclusionsThese data suggest that results obtained with one probe in vivo may not apply to another CYP3A substrate. The poor quantitative relationship between cyclosporine concentrations and the erythromycin breath test limits its usefulness in the prediction of an individual's cyclosporine dose requirementClinical Pharmacology&Therapeutics(1996)59, 4
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90023-5
年代:1996
数据来源: WILEY
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9. |
Pharmacokinetic‐pharmacodynamic relationships of controlled‐release oxycodone |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 52-61
Robert F. Kaiko,
David P. Benziger,
Ronald D. Fitzmartin,
Brian E. Burke,
Robert F. Reder,
Paul D. Goldenheim,
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摘要:
Plasma concentrations of oxycodone, oxymorphone, and noroxycodone were determined after administration of 20 mg oral controlled‐release oxycodone tablets to four subject groups: young (aged 21 to 45 years) men, elderly (aged 65 to 79 years) men, young women, and elderly women. Area under the oxycodone and noroxycodone concentration‐time curve (AUC) values were comparable among the four groups. Compared with oxycodone, the oxymorphone AUC values were small, with significant differences between subject groups. AUC values were also calculated for the pharmacodynamic variable “drug effect,” scored on a 100 mm visual analog scale. The two groups with the highest oxycodone AUC values (young and elderly women) had the lowest oxymorphone AUC values and the greatest drug effect AUC values. The two groups with the lowest oxycodone AUC values (young and elderly men) had the highest oxymorphone AUC values and the lowest drug effect AUC values. These results support oxycodone, and not oxymorphone, as being primarily responsible for pharmacodynamic and analgesic effects.Clinical Pharmacology&Therapeutics(1996)59, 52
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90024-7
年代:1996
数据来源: WILEY
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10. |
Grapefruit juice and its flavonoids inhibit 11β‐hydroxysteroid dehydrogenase |
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Clinical Pharmacology&Therapeutics,
Volume 59,
Issue 1,
1996,
Page 62-71
Yil Seob Lee,
Beverly J. Lorenzo,
Theo Koufis,
Marcus M. Reidenberg,
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摘要:
IntroductionThe enzyme 11β‐hydroxysteroid dehydrogenase (11β‐OHSD) oxidizes cortisol to inactive cortisone. Its congenital absence or inhibition by licorice increases cortisol levels at the mineralocorticoid receptor, causing mineralocorticoid effects. We tested the hypothesis that flavonoids found in grapefruit juice inhibit this enzyme in vitro and that grapefruit juice itself inhibits it in vivo.MethodsMicrosomes from guinea pig kidney cortex were incubated with cortisol and nicotinamide adenine dinucleotide (NAD) or nicotinamide adenie dinucleotide phosphate (NADP) and different flavonoids and the oxidation to cortisone measured with use of HPLC analysis. In addition, healthy human volunteers drank grapefruit juice, and the ratio of cortisone to cortisol in their urine was measured by HPLC and used as an index of endogenous enzyme activity.ResultsBoth forms of 11β‐OHSD requiring either NAD or NADP were inhibited in a concentration‐dependent manner by the flavonoids in grapefruit juice. Normal men who drank grapefruit juice had a fall in their urinary cortisone/cortisol ratio, suggesting in vivo inhibition of the enzyme.ConclusionDietary flavonoids can inhibit this enzyme and, at high doses, may cause an apparent mineralocorticoid effect.Clinical Pharmacology&Therapeutics(1996)59,
ISSN:0009-9236
DOI:10.1016/S0009-9236(96)90025-9
年代:1996
数据来源: WILEY
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