A comparative study of the pharmacokinetics and pharmacodynamics of atenolol, hydrochlorothiazide and amiloride in normal young and elderly subjects and elderly hypertensive patients

Sabanathan, K.; Castleden, C. M.; Adam, H. K.; Ryan, Jerome R.; Fitzsimons, Timothy J.

doi:10.1007/bf00609957

Cited by 40 publications

(14 citation statements)

References 19 publications

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“…However, the incidence of hyperkalaemia with these drugs increases with age, particularly in the presence of renal impairment (Lawson 1974). Increased plasma amiloride concentrations (Sabanathan et al 1987;Somogyi et al 1990) associated with age-related reductions in urinary potassium excretion have recently been demonstrated. No data were available on serum potassium concentrations (Somogyi et al 1990).…”

Section: Potassium-sparing Diureticsmentioning

confidence: 98%

Adverse Drug Reactions An Overview of Special Considerations in the Management of the Elderly Patient

Brawn

Castleden²

1990

Drug Safety

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The incidence of adverse drug reactions increases with aging, and the elderly are more likely to suffer serious or fatal reactions. Thus, morbidity and mortality are considerable in old patients, with 15% of those in hospital suffering a reaction, and many admitted as a consequence of one. The greater propensity of older patients for adverse drug reactions largely reflects the prescription of drugs to them, although over-the-counter purchases must also play a part. The elderly take more drugs per se (which is a reflection of multiple pathology), and more drugs with a narrow therapeutic index associated with a high risk of dangerous adverse reactions and drug interactions. They also have a reduced ability to withstand any reactions due to concomitant disease, and an altered pharmacokinetic and -dynamic response which tends to increase drug effects. The recommendation must be to use fewer drugs in older patients, perhaps trying alternative medicine first in nonacute conditions. Starting doses can often be reduced in the elderly, and clinical and therapeutic monitoring of effect is mandatory. The use of diuretics, antihypertensives, anti-Parkinsonian drugs and anticoagulants emphasise these points, and is discussed in detail together with digoxin, analgesics and nonsteroidal anti-inflammatory drugs. Clear guidelines are given for the use of each of these classes of drug.

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Section: Potassium-sparing Diureticsmentioning

confidence: 98%

Adverse Drug Reactions An Overview of Special Considerations in the Management of the Elderly Patient

Brawn

Castleden²

1990

Drug Safety

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“…A slight reduction in the renal clearance of thiazide diuretics and triamterene, alone or in combination, has also been observed with advancing age [101,102]. The latter findings have been disproved by a recent study [77].…”

Section: Diureticsmentioning

confidence: 99%

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Mangoni

Jackson

2003

Brit J Clinical Pharma

1,343

911

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Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiolog ical stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.

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“…Several studies have reported that peak plasma levels occur 4 hr after oral administration, absorption ranges from 90% to 95% of the dose and half-life ranges from 10-14 hr. [2][3][4][5] Since amiloride exhibits an extremely low therapeutic range (0.5-25 ng/mL), only a few sufficiently specific and sensitive HPLC methods for pharmacokinetic studies have been described. [6][7][8][9][10][11] The pharmacokinetics and bioavailability of amiloride in plasma and/or urine have been investigated by determining its levels by fluorometric, 12 radioactive, 13 densitofluorimetric, 14 or spectrometric 15 assays.…”

Section: Amiloridementioning

confidence: 99%

Analytical HPLC Method Validation of Amiloride and Its Pharmacokinetic Study in Humans

Myung

Bae

Kim

et al. 2008

Journal of Liquid Chromatography & Related Technologies

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This study was aimed to validate a reliable analytical method for the pharmacokinetic study of amiloride in human plasma by a high performance liquid chromatography (HPLC) system with UV detection. Triamterene was used as an internal standard. After extraction with ethylacetate, the supernatant was evaporated. Then, the residue was reconstituted and an aliquot was injected onto the HPLC system. Separation was performed on a Capcell Pak C 18 UG120 column (4.6 mm × 150 mm, 5 m particles) with a mobile phase of 12% acetonitrile containing 0.4% glacial acetic acid and UV detection at a wavelength of 360 nm. The intra-and inter-day precision expressed as the relative standard deviation was less than 15%. The flow rate of mobile phase was 1 mL/min and the retention time of amiloride and internal standard, triamterene, was found to be 3.06 and 8.80 min, respectively. The lower limit of quantification (LOQ) was 0.2 ng/mL of amiloride using 1 mL of plasma. The calibration curve was linear in the concentration range of 0.2-50 ng/mL (r 2 = 1 0000). The mean accuracy was 85.1-101.7%. The coefficient of variation (precision) in the intra-and interday validation was 2.1-12.5 and 2.4-13.7%, respectively. The pharmacokinetics of amiloride was evaluated after a single oral administration of 10 mg to healthy volunteers. The AUC 0-72hr , C max , T max , and T 1/2 were 267 7 ± 60 0 ng · hr/mL, 22 9 ± 5 4 ng/mL, 3 0 ± 0 8 hr, and 13 6 ± 2 4 hr, respectively. These results Correspondence: 2456 C. S. Myung et al.demonstrated that this method was highly feasible and reproducible for pharmacokinetic studies of amiloride in eight volunteers after oral administration (10 mg as amiloride HCl).

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A comparative study of the pharmacokinetics and pharmacodynamics of atenolol, hydrochlorothiazide and amiloride in normal young and elderly subjects and elderly hypertensive patients

Cited by 40 publications

References 19 publications

Adverse Drug Reactions An Overview of Special Considerations in the Management of the Elderly Patient

Adverse Drug Reactions An Overview of Special Considerations in the Management of the Elderly Patient

Age‐related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications

Analytical HPLC Method Validation of Amiloride and Its Pharmacokinetic Study in Humans

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