The effect of age on theophylline clearance in normal subjects.

Randolph, W.; Jj, Seaman; Dickson, Brian; Peace, KE; Frank, Werner; Young, Iain M.

doi:10.1111/j.1365-2125.1986.tb02941.x

Cited by 11 publications

(5 citation statements)

References 6 publications

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“…Randolph et al . ( 42) also reported that, compared with the youngest group (aged 18–35 years), theophylline clearance was significantly reduced in both middle‐aged (aged 36–53 years) and elderly (aged 54–70 years) subjects. Other studies have reported similar patterns ( 17, 27, 43, 44).…”

Section: Introductionmentioning

confidence: 91%

In vivoage-related changes in hepatic drug-oxidizing capacity in humans

Tanaka

1998

Journal of Clinical Pharmacy and Therapeutics

152

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SUMMARYand, therefore, it is thought that the metabolism of drugs also undergoes changes during this period (1) Very few studies have been carried out looking at how (Table 1). In particular, there can be differences in the effects of drugs and their toxicity in humans hepatic drug-oxidizing capacity in neonates (<4 change during their lifespan (developing and ageing).weeks), infants (< 12 months), children (<19 years), The purpose of this study is to review the literature young/mature adults (20-64 years) and elderly adults on the changes in probe-drug metabolism, classified (>65 years) (1). Hence, studying changes in the by cytochrome P450 (P450 or CYP) at five stages in life:activity of cytochrome P450 (P450 or CYP), the neonates < 4 weeks, infants < 12 months, children < 19 enzyme involved in drug metabolism, is extremely years, young/mature adults 20-64 years, and elderly important in order to select suitable therapy for adults >65 years. The main probe drugs include cafpatients who are developing or ageing, but also to feine and theophylline, whose metabolism is cataprevent poisoning and adverse drug reactions. lysed by CYP1A2, tolbutamide, phenytoin and Human P450 can be subdivided into many isoibuprofen, catalysed by CYP2C9, amitriptyline and enzymes and a number of studies are directed at nortriptyline, catalysed by CYP2C19, acetaminophen, understanding their role (2-27). catalysed by CYP2E1 and lidocaine, midazolam and At present, many CYP isoforms are known to be terfenadine, catalysed by 3A3/4. involved in drug metabolism (CYPlAl, CYP1A2, From the published in vivo studies two different CYP2C9 and CYP2C19, CYP2D6, CYP2E1, CYP3A4 patterns of drug metabolism can be identified: (i) and CYP3A5). CYP3A4 and CYP3A5 are the most activity is low immediately after birth, increases, abundant (in the liver and intestine) and CYP2D6 then peaks at the young/mature adult level and, and CYP2C19 are polymorphically expressed in the finally, decreases in old age (drugs catalysed by liver. Recently, we have reported on the deCYPlA2, CYP2C9, CYP2C19, CYP2D6 and CYP3A3/ velopmental expression of P450 enzymes in the 4) and (ii) activity increases rapidly after birth to human liver in vitro (28). However, to date, only a reach a level equivalent to that in the young/mature few reports have described investigations of hepatic adult, then gradually decreases and finally decreasing drug-oxidizing activity throughout the entire human faster in old age (drugs catalysed by CYP2E1).lifespan, from neonates to elderly adults, using a Further study of the changes in P450 with age is probe drug in vivo. warranted to help prevent adverse reactions and toThe purpose of this study is to review studies on guide us in tailoring therapy better for the individual the changes in probe-drug metabolism during human patient.development from birth to old age in vivo.

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Section: Introductionmentioning

confidence: 91%

In vivoage-related changes in hepatic drug-oxidizing capacity in humans

Tanaka

1998

Journal of Clinical Pharmacy and Therapeutics

152

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“…32,33 On the other hand, in vivo studies showed equivocal results (a decrease or no change) in hepatic drug clearance by different CYP isoforms in the elderly, as shown in Table 2. [17][18][19]28,29,[34][35][36][37][38][39][40][41][42][43][44][45][46] The paradoxical pattern of in vitro versus in vivo activity of CYP enzymes in the elderly for phase I drug metabolism may be explained by the oxygen delivery theory: oxygen delivery to liver microsomes is not constrained in the in vitro studies, whereas in the in vivo studies, age-related alterations in the hepatic architecture (such as thickening and defenestration of hepatic sinusoidal endothelium and deposition of collagen) may reduce oxygen availability for phase I drug metabolism. 13,29,47 On the contrary, the enzyme system responsible for metabolism of drugs by conjugation [eg, glucuronidation, sulphation, and acetylation (phase II reaction)] requires oxygen indirectly to produce energy.…”

Section: Drug Distribution In Agingmentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Crisis in the Elderly

ELDesoky¹

2007

American Journal of Therapeutics

183

107

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Advances in medical technology have led to improved survival after catastrophic illnesses. Many of the survivors require ongoing care including tracheostomy, mechanical ventilation, tube feedings, and indwelling venous catheters. Repeated hospitalizations may be necessary to treat infectious complications resulting from resistant organisms requiring intravenous antibiotic therapy. Because prolonged intravenous access may be difficult or even impossible in these patients, alternative means of therapy are necessary. Linezolid is the first of a new class of antimicrobial agents known as the oxazolidinones with activity against gram-positive bacteria similar to that of vancomycin and yet its oral bioavailability allows for enteral administration. We present our retrospective experience with oral linezolid in a cohort of pediatric intensive care unit patients. Primary infectious disease issues included endocarditis, tracheitis, pneumonia, or central line sepsis resulting from Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus, and Enterococcus. Treatment was initiated with vancomycin and changed to enteral linezolid (10 mg/kg every 12 hours). The duration of therapy with linezolid varied from 7 days to 6 weeks. All of the patients were discharged home to complete their course of enteral linezolid. No complications related to linezolid therapy were noted, and all of the patients completed their prescribed course of therapy without the need for rehospitalization. Our preliminary experience suggests that oral linezolid offers an effective alternative to intravenous vancomycin for the treatment of infections resulting from gram-positive bacteria and avoids the need for prolonged vascular access.

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“…Most serious adverse events of theophylline have been observed when the drug was overdosed. 5 However, adverse events of theophylline may develop also in patients who are taking the usual dose because the clearance of theophylline is modified by various factors, including aging, [6][7][8][9][10][11][12][13] a reduction in physiological hepatic function [14][15][16][17][18][19][20] and drug interactions with other medications. 21,22 To investigate the incidence and severity of such adverse events, we studied elderly patients who received sustainedrelease theophylline in the present large-scale prospective study.…”

Section: Article In Pressmentioning

confidence: 99%

A prospective clinical study of theophylline safety in 3810 elderly with asthma or COPD

Ohta

Fukuchi

Grouse

et al. 2004

Respiratory Medicine

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A large-scale prospective study was conducted in 3810 Japanese elderly (> or =65 years old) patients with asthma or chronic obstructive pulmonary disease (COPD) who had been treated with sustained-release theophylline tablets (THEODUR) at a dose of 400 mg/day for 1-6 months, in principle. Among 3798 protocol-complying patients (mean age: 73.8 +/- 0.10 years, 1997 with COPD), 261 theophylline-related adverse events were observed in 179 (4.71%) patients. The 5 most frequently observed adverse events were "nausea" (40 episodes, 1.05%), "loss of appetite" (22 episodes, 0.56%), "hyperuricemia" (16 episodes, 0.42%), "palpitation" (15 episodes, 0.39%), and "increased alkaline phosphatase" (11 episodes, 0.28%). No convulsions were reported. Six patients had serious adverse events. The incidence of theophylline-related adverse events was higher in patients with hepatic disease (odds ratio: 1:1.81) and in patients with arrhythmia (odds ratio: 1:1.88). Blood drug concentration measurements in 736 patients indicated that the drug levels were < or =15 microg/ml in 641 patients (87.1%), and no correlation was noted between dose and theophylline-related adverse events. These results suggest that sustained-release theophylline can be used safely in elderly patients with asthma or COPD.

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The effect of age on theophylline clearance in normal subjects.

Cited by 11 publications

References 6 publications

In vivoage-related changes in hepatic drug-oxidizing capacity in humans

In vivoage-related changes in hepatic drug-oxidizing capacity in humans

Pharmacokinetic-Pharmacodynamic Crisis in the Elderly

A prospective clinical study of theophylline safety in 3810 elderly with asthma or COPD

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