Disposition of Antipyrine and Phenytoin Correlated with Age and Liver Volume in Man

Bach, Bodil; Hansen, J. Mølholm; Kampmann, Jens P.; Rasmussen, S. N.; Skovsted, L.

doi:10.2165/00003088-198106050-00005

Cited by 105 publications

(38 citation statements)

References 29 publications

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“…However, the change in the volume of distribution and slightly higher clearance may reflect alterations in protein binding. It has been shown that plasma concentrations of albumin decrease with age (Woodford-Williams et al, 1964) leading to changes in free drug fraction and consequently to changes in clearance and volume of distribution (Greenblatt et al, 1980 (Triggs & Nation, 1975;Hayes et al, 1975;Bach et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

The pharmacokinetics of doxazosin in elderly normotensives.

Vincent¹,

Modesti²,

Elliott³

et al. 1986

Brit J Clinical Pharma

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The pharmacokinetics of doxazosin were studied in 12 normotensive elderly volunteers aged 62-89 years. There was marked inter-individual variability in all the parameters derived but the disposition of doxazosin was similar in both sexes. These results were compared to those of a group of young normotensive volunteers aged 23-39 years studied previously under comparable conditions. The volume of distribution increased significantly with age although the bioavailability and clearance were not significantly different in the two groups. These results suggest that age is unlikely to influence the disposition of doxazosin to a clinically significant extent.

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Section: Discussionmentioning

confidence: 99%

The pharmacokinetics of doxazosin in elderly normotensives.

Vincent¹,

Modesti²,

Elliott³

et al. 1986

Brit J Clinical Pharma

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“…In contrast to elderly individuals (older than 65 years, who have a decreased capacity to metabolize phenytoin because of age-related losses in liver functionality), [24][25] pregnant women taking phenytoin have increased dosage requirements, particularly during the third trimester. [26][27][28][29] The main reason for this change is that, although both have decreased protein binding due to low albumin concentrations (hypoalbuminemia) and consequently increased unbound fraction in plasma, pregnant women usually show increased metabolism of phenytoin (apart from a decreased bioavailability due to malabsorption).…”

Section: Bringing Theory To the Clinical Setting: Application To A Rementioning

confidence: 99%

Applying Organ Clearance Concepts in a Clinical Setting

Duconge¹

2008

Am J Pharm Educ

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Objective. To teach doctor of pharmacy (PharmD) students how to apply organ clearance concepts in a clinical setting in order to optimize dose management, select the right drug product, and promote better patient-centered care practices. Design. A student-focused 5-hour topic entitled "Organ Clearance Concepts: Modeling and Clinical Applications" was developed and delivered to second-year PharmD students. Active-learning techniques, such as reading assignments and thought-provoking questions, and collaborative learning techniques, such as small groups, were used. Student learning was assessed using application cards and a minute paper. Assessment. Overall student responses to topic presentation were overwhelmingly positive. The teaching strategies here discussed allowed students to play an active role in their own learning process and provided the necessary connection to keep them motivated, as mentioned in the application cards and minute paper assessments. Students scored an average of 88% on the examination given at the end of the course. Conclusion. By incorporating active-learning and collaborative-learning techniques in presenting material on organ clearance concept, students gained a more thorough knowledge of dose management and drug-drug interactions than if the concepts had been presented using a traditional lecture format. This knowledge will help students in solving critical patient situations in a real-world context. INTRODUCTIONTeaching strategies to ensure students' adeptness in critical thinking and problem solving need to be an integral part of the PharmD curriculum. A topic entitled ''Organ Clearance Concepts: Modeling and Clinical Applications,'' offered in the PharmD program of the University of Puerto Rico School of Pharmacy (UPR-SP) in the last 2 academic years is described and its outcomes discussed. This curricular effort followed a smooth transition from dependent to independent learning and involved PharmD students as active, self-directed learners in solving problems related to clinical pharmacokinetics that are commonly encountered in the practice of pharmacy.Clearance, the parameter which relates rate of elimination to drug concentration, is important because it defines the rate of administration required to maintain a plateau drug concentration. Together with the extent of distribution outside of plasma, clearance also determines the speed at which a drug is eliminated from the body.1-2 The sensitivity of organ clearance of a drug to changes in binding within blood depends on its unbound clearance. If unbound clearance is low, relative to organ blood flow, the extraction ratio (and clearance) will always be low and dependent on plasma binding. [1][2][3] If the extraction ratio is high, elimination becomes perfusion rate-limited and clearance will be relatively insensitive to changes in binding, but oral bioavailability may exhibit dependence on binding if the liver is the major eliminating organ.1-4 A full insight into the implications of altered binding on pharmacokinetics requires...

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“…In a manner similar to the kidney, the liver undergoes a number of changes with age that includes a reduction in blood flow (31) and mass (or volume) (32,33). Reduced blood flow might suggest a reduction in the clearance of those compounds with a high hepatic clearance (or high extraction ratio, nonrestrictively cleared).…”

Section: Hepatic Metabolismmentioning

confidence: 99%

“…It is more difficult to interpret the changes in liver mass. Several studies have shown a direct correlation between liver mass and clearance of compounds with a low clearance and that undergo oxidative metabolism (antipyrine and phenytoin) (33,34 Figure 6. Antipyrine clearance as a function of age in 307 healthy male subjects reason for this is the fact that half-life is a parameter dependent on clearance and volume of distribution.…”

Section: Hepatic Metabolismmentioning

confidence: 99%

Pharmacokinetics in the Elderly

1982

Inpharma

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Animals undergo substantial changes in many physiologic and biochemical functions as a natural consequence of aging. In the absence of disease or other pathologic conditions, these changes occur in a gradual manner with time (generally expressed as a fractional or percentage change in that function per year or decade). Furthermore, for any given function and at any given chronologic age, there is large variation in that function among individuals. Given the increase in life expectancy, the substantial increase in the number of elderly (and aged elderly) in the population, and the escalating costs of health care, there is great interest in learning more about the risks associated with aging as a result of toxic exposure. Are the elderly at greater risk than younger adults to the toxic effects of drugs and environmental exposure? Is the elderly population an inherently more sensitive one?

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Disposition of Antipyrine and Phenytoin Correlated with Age and Liver Volume in Man

Cited by 105 publications

References 29 publications

The pharmacokinetics of doxazosin in elderly normotensives.

The pharmacokinetics of doxazosin in elderly normotensives.

Applying Organ Clearance Concepts in a Clinical Setting

Pharmacokinetics in the Elderly

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