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1. |
Transcutaneous theophylline collection in preterm infants |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 427-434
M Gail Murphy,
Carl C Peck,
Dale P Conner,
Kaveh Zamani,
Gerald B Merenstein,
Donna Rodden,
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摘要:
Transcutaneous collection of theophylline and its metabolite, caffeine, was undertaken in 33 preterm infants (2 to 89 days old) who were receiving routine theophylline therapy. Collection was done by means of a novel adhesive transcutaneous collection system. The transcutaneous collection system accumulated substances that migrated from the blood to the skin surface by trapping them in an activated charcoal‐gel matrix. On one to three occasions, four transdermal collection systems were applied to the back or abdomen of each infant for 4 to 12 hours. During that time, blood samples were obtained for routine monitoring of plasma theophylline levels. Amounts of theophylline (95 ± 198 ng) and caffeine (83 ± 77 ng) in the transcutaneous collection system were significantly correlated with the respective average plasma drug concentration and postconceptional age (p<0.01). Skin reactions were limited to mild erythema. We concluded that theophylline and caffeine can be collected on the surface of the skin of preterm infants with a novel transcutaneous collection system. Amounts collected by means of the transcutaneous collection system correlated with plasma concentrations consistent with a diffusion process, but they were poor predictors of individual concentrations.Clinical Pharmacology and Therapeutics(1990)47,427–434; doi:10.1038/clpt.1
ISSN:0009-9236
DOI:10.1038/clpt.1990.53
年代:1990
数据来源: WILEY
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2. |
The effects of theophylline and nifedipine on corticotropin‐stimulated cortisol secretion |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 435-438
Michael T McDermott,
Tony L Walden,
Michael Bornemann,
Robert J Sjoberg,
Fred D Hofeldt,
Gerald S Kidd,
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摘要:
The adrenal cortisol response to corticotropin appears to involve both calcium and cyclic adenosine 3′,5′‐monophosphate (cAMP) as intracellular mediators. In 10 healthy male volunteers, the short‐term administration of theophylline, which affects both intracellular calcium and cAMP, lowered basal cortisol levels but augmented the in vivo cortisol response to short‐term corticotropin stimulation. Short‐term administration of nifedipine, a calcium channel antagonist, had no effect on basal or peak cortisol levels but reduced the incremental cortisol response to corticotropin. The effects of both theophylline and nifedipine, although statistically significant, were modest and of questionable clinical significance but should be considered in the interpretation of the clinical corticotropin stimulation test. They may also provide some insight into the post‐receptor actions of corticotropin.Clinical Pharmacology and Therapeutics(1990)47,435–438; doi:10.1
ISSN:0009-9236
DOI:10.1038/clpt.1990.54
年代:1990
数据来源: WILEY
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3. |
Influence of tretinoin on the percutaneous absorption of minoxidil from an aqueous topical solution |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 439-446
James J Ferry,
Kristi K Forbes,
James T VanderLugt,
Gregory J Szpunar,
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摘要:
Nineteen healthy male volunteers completed a three‐way, randomized, crossover study to determine the effect of the synthetic retinoid, tretinoin, on percutaneous absorption of minoxidil. Subjects received, for 20 days, twice‐daily administrations of 1 ml of an aqueous 2% topical minoxidil solution either alone, with once‐daily applications of a 0.05% tretinoin cream, or with once‐daily applications of a vehicle control cream. When minoxidil was coadministered with tretinoin cream, minoxidil absorption was increased nearly threefold, compared with a 1.3‐fold increase in absorption observed with coadministration of vehicle control cream. Transepidermal water loss measurements, which are sensitive to changes in stratum corneum function, were also significantly increased with tretinoin. No treatment‐related changes in stratum corneum thickness were observed on the basis of skin biopsy analysis. The findings indicate that percutaneous minoxidil absorption is enhanced by tretinoin as a result of increased stratum corneum permeability.Clinical Pharmacology and Therapeutics(1990)47,439–446; doi:10.103
ISSN:0009-9236
DOI:10.1038/clpt.1990.55
年代:1990
数据来源: WILEY
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4. |
Effects of age on the protein binding and disposition of propranolol stereoisomers |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 447-455
Richard L Lalonde,
David M Tenero,
Brad S Burlew,
Vanessa L Herring,
Michael B Bottorff,
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摘要:
Previous studies of the effects of age on the disposition of propranolol have produced variable results. We evaluated the stereoselective disposition and protein binding of propranolol enantiomers in 10 young (mean age, 28 years) and 10 older (mean age, 64 years) healthy subjects. After receiving racemic propranolol orally for 6 days, the oral clearances of d‐propranolol and 1‐propranolol were lower by 13% and 17% in the older group compared to the young group, but these differences were not statistically significant. The older subjects had higher α1‐acid glycoprotein concentrations (p<0.05) and lower unbound fractions of 1‐propranolol (p<0.05). After protein binding was accounted for, the unbound oral clearance of each enantiomer was similar in both groups. 1‐Propranolol was more highly protein bound than d‐propranolol (p<0.05) in both young and older subjects. The unbound oral clearance d/1 ratio was not different from unity in either group, indicating that the stereoselective differences in oral clearance were largely attributable to the stereoselective differences in protein binding.Clinical Pharmacology and Therapeutics(1990)47,447–455; doi:10.10
ISSN:0009-9236
DOI:10.1038/clpt.1990.56
年代:1990
数据来源: WILEY
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5. |
Inhibitory effects of the new PAF acether antagonist WEB‐2086 on pharmacologic changes induced by PAF inhalation in human beings |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 456-462
Waclaw S Adamus,
Hubert O Heuer,
Christopher J Meade,
Johann C Schilling,
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摘要:
Recent research on asthma mediators has concentrated more and more on platelet‐activating factor (PAF), which is one of the most potent bronchoconstrictors known thus far. Inhalant PAF challenge in healthy volunteers may provide a mean of testing PAF antagonists. The usefulness of the PAF provocation test in measuring the pharmacologic activity of a new PAF antagonist, WEB‐2086, has been examined in 12 healthy volunteers in a double‐blind, placebo‐controlled, within‐subject crossover study. PAF‐induced immediate bronchoconstriction, slight hemodynamic changes, and PAF‐related subjective side effects. Premedication with WEB‐2086 (40 mg) completely prevented any increase in airway resistance after PAF inhalation, as well as development of most of the cardiovascular and side effects induced by PAF. The clear protection against PAF‐induced pharmacologic effects can be explained by the specific PAF‐antagonistic activity of WEB‐2086. The method described in this article may be applied as a useful tool for looking at PAF‐antagonistic activity in healthy volunteers.Clinical Pharmacology and Therapeutics(1990)47,456–462
ISSN:0009-9236
DOI:10.1038/clpt.1990.57
年代:1990
数据来源: WILEY
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6. |
The effect of hepatic cirrhosis on the pharmacokinetics and blood pressure response to nicardipine |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 463-469
T A Razak,
J J McNeil,
R B Sewell,
O H Drummer,
R A Smallwood,
E L Conway,
W J Louis,
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摘要:
The present study was designed to compare the pharmacokinetic handling of a single oral dose of nicardipine in normal subjects and in patients with hepatic cirrhosis and to compare the sensitivity of the two groups to its hypotensive effect. Nicardipine plasma concentrations were substantially higher in the subjects with hepatic cirrhosis with impaired antipyrine clearance, as shown by a significantly higher average Cmaxand AUC. The terminal elimination half‐life in this group varied from 0.8 to 60.2 hours (median, 11.7 hours), compared with 0.6 to 4.1 hours (median, 1.4 hours) in the group of eight subjects with normal liver function. In the cirrhotic patients with impaired antipyrine clearance, the AUC of the pyridine metabolite averaged 10% of that of the parent drug, whereas in normal subjects the ratio averaged 48%. This finding suggests less conversion of nicardipine to this metabolite in subjects with impaired hepatic function. Peak blood pressure decreases were greater in the cirrhotic group, which was in keeping with the higher plasma levels in these subjects.Clinical Pharmacology and Therapeutics(1990)47,463–469; doi:10.1038/clpt.199
ISSN:0009-9236
DOI:10.1038/clpt.1990.58
年代:1990
数据来源: WILEY
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7. |
HumanN‐acetylation genotype determination with urinary caffeine metabolites |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 470-477
Anthony J Kilbane,
Lawrence K Silbart,
Melanie Manis,
Inese Z Beitins,
Wendell W Weber,
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摘要:
The human acetylation genotype was determined by measuring urinary caffeine metabolites by use of a modification of a previously published HPLC method. The problem of separation of 7‐methylxanthine (7X) from 1‐methyluric acid (1U) in urine extracts was achieved by adding a phenyl column, in tandem with a C18reverse‐phase column, by means of a methanol:aqueous acetic acid gradient elution system. The urinary molar ratios of (AAMU)/(AAMU + 1U + 1X) and (AAMU)/(1X) were estimated in 20 subjects phenotyped with dapsone, with 100% concordance for the [AAMU]/[1X]ratio. A population study of 42 unrelated individuals exhibited trimodal distribution in acetylation capacity, consistent with the Hardy‐Weinberg theory of population genetics. Definitive pedigree analysis of 16 families (75 subjects) resulted in significant similarity between the observed genotypic matings and those expected by classical Mendelian segregation. This noninvasive genotyping method promises to be useful in future investigation of the relationship between the human acetylation polymorphism and clinical disorders.Clinical Pharmacology and Therapeutics(1990)47,470–477; doi:10.1038/cl
ISSN:0009-9236
DOI:10.1038/clpt.1990.59
年代:1990
数据来源: WILEY
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8. |
Comparison of deferoxamine pharmacokinetics between asymptomatic thalassemic children and those exhibiting severe neurotoxicity |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 478-482
Yedidia Bentur,
Gideon Koren,
Angelo Tesoro,
Holly Carley,
Nancy Olivieri,
Melvin H Freedman,
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摘要:
The use of deferoxamine for iron chelation in transfusion‐dependent thalassemia major is limited by serious neurotoxicity (hearing and vision loss). We assessed whether interpatient variability in handling deferoxamine and resultant accumulation of the drug may account for the neurotoxicity. We studied steady‐state deferoxamine pharmacokinetics during intravenous infusion in two groups of patients—one group exhibited severe manifestations of auditory and visual loss and one group was asymptomatic. The groups were matched for age, sex distribution, weight, treatment period, ferritin levels, and hemoglobin levels. Similarly, doses of deferoxamine at the time of the study were not different. Clearance rates were not different between the symptomatic and asymptomatic patients (39.83 ± 4.54 versus 30.66 ± 4.39 ml/min · kg). However, patients who exhibited toxicity received significantly higher daily doses of subcutaneous deferoxamine at the time of diagnosis of neurotoxicity (9.03 ± 0.96 and 5.58 ± 0.61 mg/kg · hr, respectively;p<0.005). These data suggest that deferoxamine induced neurotoxicity is dose‐dependent and cannot be attributed to accumulation of the drug caused by slower clearance rates.Clinical Pharmacology and Therapeutics(1990)47,478–482; doi:10.1
ISSN:0009-9236
DOI:10.1038/clpt.1990.60
年代:1990
数据来源: WILEY
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9. |
The effect of captopril on thallium 201 myocardial perfusion in systemic sclerosis |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 483-489
André Kahan,
Jean Y Devaux,
Bernard Amor,
Charles J Menkès,
Simon Weber,
Alain Venot,
Georges Strauch,
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摘要:
In systemic sclerosis, abnormalities of myocardial perfusion are common and may be caused by a disturbance of the coronary microcirculation. We evaluated the long‐term effect of captopril (75 to 150 mg per day) on thallium 201 myocardial perfusion in 12 normotensive patients with systemic sclerosis. Captopril significantly decreased the mean (±SD) number of segments with thallium 201 myocardial perfusion defects (6.5 ± 1.9 at baseline and 4.4 ± 2.7 after 1 year of treatment with captopril;p<0.02) and increased the mean global thallium score (9.6 ± 1.7 at baseline and 11.4 ± 2.1 after captopril;p<0.05). In a control group of eight normotensive patients with systemic sclerosis who did not receive captopril, no significant modification in thallium results occurred. Side effects with captopril included hypotension (six patients), taste disturbances (one patient), and skin rash (one patient). These side effects subsided when the dosage was reduced. These findings demonstrate that captopril improves thallium 201 myocardial perfusion in patients with systemic sclerosis and may therefore have a beneficial effect on scleroderma myocardial disease.Clinical Pharmacology and Therapeutics(1990)47,483–489; doi:10.1038/clp
ISSN:0009-9236
DOI:10.1038/clpt.1990.61
年代:1990
数据来源: WILEY
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10. |
Fluoxetine differentially alters alcohol intake and other consummatory behaviors in problem drinkers |
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Clinical Pharmacology&Therapeutics,
Volume 47,
Issue 4,
1990,
Page 490-498
Claudio A Naranjo,
Karen E Kadlec,
Pablo Sanhueza,
Denise Woodley‐Remus,
Edward M Sellers,
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摘要:
The effects of fluoxetine, a relatively selective long‐acting serotonin uptake inhibitor, on the consumption of alcoholic and nonalcoholic drinks, cigarette smoking, and body weight were assessed in 29 men who were early stage problem drinkers. After a 2‐week baseline, subjects were randomly assigned to receive 40 mg/day fluoxetine (n= 8), 60 mg/day fluoxetine (n= 11), or placebo (n= 10) for 4 weeks. Fluoxetine 60 mg/day decreased mean daily alcoholic drinks from (X̄± SEM) 8.3 ± 0.7 during baseline to 6.9 ± 0.7 and decreased total drinks per 14 days from 115.8 ± 9.3 to 96.5 ± 9.5 (p<0.01; 17.3% decrease from baseline), with no significant increase in days of abstinence. Neither 40 mg/day fluoxetine nor placebo had effects on intake of alcohol. Fluoxetine 60 mg/day decreased total and mean daily alcoholic drinks compared with 40 mg/day fluoxetine (ANCOVA, bothp<0.02), but neither dose of fluoxetine was different from placebo. Compared with placebo, both 40 mg/day fluoxetine and 60 mg/day fluoxetine decreased the variability of the baseline to treatment changes in alcoholic drinks (bothp<0.05). Although no differences were detected between treatment groups, 60 mg/day fluoxetine increased mean daily nonalcoholic beverages from baseline (5.0 ± 0.4 to 5.6 ± 0.3,p<0.01) and increased daily cigarettes smoked (from 25.1 ± 4.6 to 26.9 ± 4.5,p<0.05), whereas no significant changes from baseline were observed with 40 mg/day fluoxetine or placebo. Body weight decreased with both 40 mg/day fluoxetine (from 75.7 ± 4.7 kg to 73.8 ± 4.6 kg,p<0.01) and 60 mg/day fluoxetine (from 81.4 ± 2.6 kg to 79.2 ± 2.5 kg,p<0.05) but not with placebo. Patterns of response varied, but decreases in alcohol consumption were not related to side effects, an alcohol‐sensitizing reaction, or changes in depression or anxiety. Our findings with men who are problem drinkers indicate that fluoxetine differentially alters consummatory behaviors. The reductions in alcohol intake and body weight are of clinical importance.Clinical Pharmacology and Therapeutics(1990)47,490–498; do
ISSN:0009-9236
DOI:10.1038/clpt.1990.62
年代:1990
数据来源: WILEY
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