Abstract:
:There are many pathological changes in patients with cystic fibrosis (CF) which can lead to alterations in drug disposition. Although, in patients with CF, the extent of drug absorption varies widely and the rate of absorption is slower, bioavailability is not altered. Plasma protein binding for the majority of drugs studied did not differ in patients with CF compared with control groups. The difference in volume of distribution of most drugs between patients with CF and healthy individuals vanished when corrected for lean body mass. Despite hepatic dysfunction, patients with CF have enhanced clearance of many, but not all, drugs. Phase I mixed-function oxidases are selectively affected: cytochrome P450 (CYP) 1A2 and CYP2C8 have enhanced activity, while other CYP isoforms such as CYP2C9 and CYP3A4 are unaffected. Increased phase II activities are also demonstrated: glucuronyl transferase, acetyl transferase (NAT1) and sulfotransferase. The increased hepatic clearance of drugs in the presence of CF may be the consequence of disease-specific changes in both enzyme activity and/or drug transport within the liver. The renal clearance (CLR) of many drugs in patients with CF is enhanced although there has been no pathological abnormality identified which could explain this finding: glomerular filtration rate and tubular secretion appear normal in patients with CF. The precise mechanisms for enhanced drug clearance in patients with CF remain to be elucidated. The optimisation of antibiotic therapy in patients with CF includes increasing the dose of beta-lactams by 20 to 30% and monitoring plasma concentrations of aminoglycosides. The appropriate dosage of quinolones has not been definitively established.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Rey E,Tréluyer JM,Pons Gdoi
10.2165/00003088-199835040-00004subject
Has Abstractpub_date
1998-10-01 00:00:00pages
313-29issue
4eissn
0312-5963issn
1179-1926journal_volume
35pub_type
杂志文章,评审abstract:INTRODUCTION:Neglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of ph...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
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更新日期:2017-06-01 00:00:00
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journal_title:Clinical pharmacokinetics
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Clinical pharmacokinetics
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2014-05-01 00:00:00
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更新日期:1999-01-01 00:00:00
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journal_title:Clinical pharmacokinetics
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更新日期:1991-03-01 00:00:00
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更新日期:1998-08-01 00:00:00
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abstract:BACKGROUND:International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines emphasize the need for better understanding of the influence of ethnicity on drug response to minimize duplication of clinical studies, thereby expediting drug approval. OBJ...
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abstract::Carboplatin shares some of the therapeutic advantages of cisplatin, but without a significant incidence of the dose-limiting neurotoxicity and nephrotoxicity which is experienced with cisplatin. However, its use is associated with dose-limiting bone marrow suppression. Carboplatin is present in the blood as 3 distinct...
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