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1. |
Clinical pharmacology comes of age |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 485-488
Terrence F Blaschke,
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摘要:
Clinical Pharmacology and Therapeutics(1989)46,485–488; doi:10.1038/clpt.1989.1
ISSN:0009-9236
DOI:10.1038/clpt.1989.174
年代:1989
数据来源: WILEY
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2. |
The state of pediatric clinical pharmacology: An international survey of training programs |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 489-493
Gideon Koren,
Stuart M Macleod,
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摘要:
Clinical Pharmacology and Therapeutics(1989)46,489–493; doi:10.1038/clpt.1989.1
ISSN:0009-9236
DOI:10.1038/clpt.1989.175
年代:1989
数据来源: WILEY
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3. |
Alteration of zidovudine pharmacokinetics by probenecid in patients with AIDS or AIDS‐related complex |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 494-499
Paulo Miranda,
Steven S Good,
Robert Yarchoan,
Rose V Thomas,
M Robert Blum,
Charles E Myers,
Samuel Broder,
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摘要:
The anti–human immunodeficiency virus drug zidovudine is metabolized extensively in human beings to the 5′‐glucuronide (GAZT) and is cleared rapidly, resulting in a short half‐life and the need for frequent dosing. This study explores whether probenecid, which is also metabolized by glucuronidation, reduces zidovudine clearance when zidovudine is adminstered orally to patients with acquired immunodeficiency syndrome (AIDS) or AIDS‐related complex (ARC). The mean zidovudine plasma levels were significantly higher after concurrent administration of probenecid than in its absence, resulting in a twofold increase in the mean AUC, a corresponding decline in the apparent total clearance, and a prolongation in the mean half‐life. Similar alterations were observed in GAZT disposition. There was a marked reduction in the urinary excretion ratio of GAZT to zidovudine and a decline in the renal clearance of GAZT after probenecid coadministration. Probenecid inhibits zidovudine glucuronidation and renal excretion of GAZT.Clinical Pharmacology and Therapeutics(1989)46,494–499; doi:10.1038
ISSN:0009-9236
DOI:10.1038/clpt.1989.176
年代:1989
数据来源: WILEY
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4. |
Correction |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 500-500
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摘要:
Clinical Pharmacology and Therapeutics(1989)46,500; doi:10.1038/clpt.1989.177
ISSN:0009-9236
DOI:10.1038/clpt.1989.177
年代:1989
数据来源: WILEY
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5. |
Sulfation pharmacogenetics: Correlation of human platelet and small intestinal phenol sulfotransferase |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 501-509
Rajah S Sundaram,
Jon A Van Loon,
Richard Tucker,
Richard M Weinshilboum,
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摘要:
Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of phenolic drugs. All human tissues studied contain a thermostable (TS) form of PST, which catalyzes the sulfate conjugation of “simple” phenols such asp‐nitrophenol, and a thermolabile (TL) form, which catalyzes the sulfation of dopamine and other monoamines. In the present study we tested the hypothesis that genetically controlled levels of TS and TL PST activity in the platelet, as well as inherited variations in the thermal stability of platelet TS PST, might reflect those same characteristics of the enzyme in a less accessible tissue, human small intestinal mucosa. Platelet TS and TL PST activities and TS PST thermal stability were measured in blood samples from 45 randomly selected healthy subjects, and 14 of those subjects were selected to have intestinal biopsies performed. There was a significant correlation between levels of platelet and jejunal mucosal TS PST activity (rs= 0.574,p<0.030), but there was not a significant correlation between levels of TL PST activity in the two tissues (rs= 0.265,p= 0.368). There was also a significant correlation between the trait of TS PST thermal stability in the two tissues (rs= 0.828,p<0.0001). These observations suggest that inherited variations in TS PST activity and thermal stability in an easily obtained tissue, the platelet, might be used to predict individual differences of those properties of the enzyme in the human small intestine, an organ that plays an important role in drug metabolism.Clinical Pharmacology and Therapeutics(1989)46,501–509; doi:10.1038/clpt.
ISSN:0009-9236
DOI:10.1038/clpt.1989.178
年代:1989
数据来源: WILEY
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6. |
Fasting plasma homocysteine as a sensitive parameter of antifolate effect: A study of psoriasis patients receiving low‐dose methotrexate treatment |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 510-520
Helga Refsum,
Svein Helland,
Per M Ueland,
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摘要:
We have investigated the effect of low‐dose methotrexate (25 mg weekly) on plasma homocysteine in 13 patients who had psoriasis. Total, free, and protein‐bound homocysteine were determined both during fasting and after methionine loading. Psoriasis patients had significantly higher basal plasma homocysteine levels than age‐matched control subjects. In addition, the methionine loading test was abnormal in four of the patients, but this was not significant. Psoriasis patients, although not folate deficient, did have lower serum folate levels than control subjects. There was a significant and transient increase in fasting plasma homocysteine levels within 48 hours after administration of low‐dose methotrexate. This response was repeated after each administration and was observed eight to 20 times in three patients whose progress was monitored for 2 to 6 months. Notably, methotrexate did not affect the plasma profile for homocysteine after methionine loading. This study showed the level of fasting plasma homocysteine to be a sensitive and responsive parameter of antifolate drug treatment.Clinical Pharmacology and Therapeutics(1989)46,510–520; doi:10.1038/clp
ISSN:0009-9236
DOI:10.1038/clpt.1989.179
年代:1989
数据来源: WILEY
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7. |
Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4 |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 521-527
Mario J Bargetzi,
Toshifumi Aoyama,
Frank J Gonzalez,
Urs A Meyer,
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摘要:
The metabolism of lidocaine to its major metabolite monoethylglycinexylidide (MEGX) was studied in human liver microsomes of 13 kidney transplant donors and of one patient with liver cirrhosis. Interindividual variation in metabolite formation was considerable. Biphasic kinetics indicated the involvement of at least two distinct enzymatic activities. With use of a series of antisera that recognize different human cytochrome P450 isozymes, we were able to identify an enzyme of the P450III gene family as one of two enzymes. By expressing human P450IIIA4 complementary deoxyribonucleic acid (cDNA) in HepG2 cells, we directly demonstrated lidocaine‐deethylase activity for this P450 isozyme. These data suggest that P450IIIA4 is at least in part responsible for microsomal MEGX formation.Clinical Pharmacology and Therapeutics(1989)46,521–527; doi:10.1038/clpt.1989
ISSN:0009-9236
DOI:10.1038/clpt.1989.180
年代:1989
数据来源: WILEY
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8. |
Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 528-536
Rainer Schulz,
Karl‐Heinz Antonin,
Edgar Hoffmann,
Maria Jedrychowski,
Eric Nilsson,
Christina Schick,
Peter R Bieck,
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摘要:
The effect of the monoamine oxidase inhibitor selegiline on tyramine metabolism and intravenous and oral tyramine pressor sensitivity was studied in healthy subjects. After oral doses of tyramine, which caused systolic blood pressure to increase by 30 mm Hg, we determined plasma concentrations ofp‐hydroxyphenylacetic acid (HPAA) and of conjugated and unconjugated tyramine. When 20 mg/day of selegiline was administered, the AUCspecof HPAA decreased from 86% to 64% and the AUCspecof conjugated tyramine increased from 13% to 35% of the sum of total tyramine and HPAA. Pressor sensitivity was enhanced more with oral administration of tyramine than with intravenous administration of tyramine. After the drug was discontinued, initial values were reached within 4 days (one subject) and 2 weeks (two subjects). Fifty‐five percent of the selegiline dose was eliminated in urine as amphetamine and methamphetamine. The findings support the assumption that selegiline does not selectively inhibit monoamine oxidase‐B (MAO‐B) when administered in doses of 20 mg/day and higher.Clinical Pharmacology and Therapeutics(1989)46,528–536; doi:10.1038/clp
ISSN:0009-9236
DOI:10.1038/clpt.1989.181
年代:1989
数据来源: WILEY
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9. |
Decreased plasma albumin concentration results in increased volume of distribution and decreased elimination of midazolam in intensive care patients |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 537-543
Tom B Vree,
Minoru Shimoda,
Jacques J Driessen,
Pieter J M Guelen,
Tom J Janssen,
Emiel F S Termond,
Roelof Dalen,
Jan C M Hafkenscheid,
Marijcke S C Dirksen,
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摘要:
The pharmacokinetic parameters of 16 patients in the intensive care unit, sedated with midazolam, were evaluated. A large variation was observed in the plasma concentration of midazolam and between the plasma concentration of midazolam and its metabolite 1‐hydroxymethylmidazolam glucuronide. The plasma albumin concentration governs the volume of distribution of midazolam. Decreased plasma albumin concentration (25 gm/L) results in an increased volume of distribution and a decreased elimination rate of midazolam. The observed plasma concentration ratio between the parent drug and its metabolite 1‐hydroxymethylmidazolam glucuronide is governed by the variables of protein binding, the metabolic rate of midazolam, and the renal clearance of the glucuronide metabolite itself (which can be considered as a measure of the kidney function of the patient).Clinical Pharmacology and Therapeutics(1989)46,537–543; doi:10.1038/clpt.19
ISSN:0009-9236
DOI:10.1038/clpt.1989.182
年代:1989
数据来源: WILEY
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10. |
Correction |
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Clinical Pharmacology&Therapeutics,
Volume 46,
Issue 5,
1989,
Page 544-544
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摘要:
Clinical Pharmacology and Therapeutics(1989)46,544; doi:10.1038/clpt.1989.183
ISSN:0009-9236
DOI:10.1038/clpt.1989.183
年代:1989
数据来源: WILEY
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