Summary
As a target group, geriataric patients were selected for pharmacokinetic studies with terodiline (Mictrol), an anticholinergic and calcium antagonist drug effective in the treatment of urinary incontinence. The single-dose kinetics in the geriatric patients (mean age 82 years) differed significantly from that previously found (Hallén et al. 1987) in healthy volunteers (mean age 35 years). There were higher peak serum concentrations (110 vs 79 µg·l−1), increased half-life (189 vs 60 h), lower renal clearance (4.0 vs 10.9 ml·min−1) and lower total clearance (29 vs 75 ml·min−1). Multiple-doses of 12.5 mg b.d. for 6–8 weeks resulted in a mean steady-state concentration of 642 µg·l−1, which was in agreement with the single dose parameters. The studied geriatric patients can be characterized not only as old, but also as frail, bedridden, having several diseases and polymedicated. The differences in pharmacokinetics between younger and elderly subjects can be attributed to a variety of complex factors, which may alter the clearance and/or the volume of distribution.
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Altman PL, Dittmer DS (1961) Blood and other body fluids. Federation of American Societies for Experimental Biology, Washington, DC, p 500
Avram MJ, Henthorn TK, Shanks CA, Krejcie TC (1986) The initial rate of change in distribution volume is the sum of intercompartmental clearances. J Pharm Sci 75: 919–920
Beisland HO, Fossberg E (1985) The effects of terodiline and meladrazin on severe motor urge incontinence in geriatric patients. J Am Geriatr Soc 33: 29–32
Blain PG, Mucklow JC, Rawlins MD, Roberts DF, Routleage PA, Shand DG (1981) Determinants of α1-acid glycoprotein concentration in health. Br J Clin Pharmacol 12: 275P
Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41
Fischer-Rasmussen W and The Multicentre Study Group (1984) Evaluation of long-term safety and clinical benefit of terodiline in women with urgency/urge incontinence — a multicentre study. Scand J Urol Nephrol 87 [Suppl]: 35–47
Gibaldi M, Perrier D (1982) Pharmacokinetics. Marcel Dekker, New York Basel, pp 445–449
Hallén B, Guilbaud O, Strömberg S, Lindeke B (1987) Singledose pharmacokinetics of terodiline, including a stable isotope technique for improvement of statistical evaluations. Biopharm Drug Dispos (in press)
Ilsalo E, Kangas L, Ruikka I (1977) Pharmacokinetics of nitrazepam in young volunteers and aged patients. Br J Clin Pharmacol 4: 646P-647P
Karlén B, Andersson K-E, Ekman G, Strömberg S, Ulmsten U (1982) Pharmacokinetics of terodiline in human volunteers. Eur J Clin Pharmacol 23: 267–270
Klotz U, Avant GR, Hoyumpa A, Schenker S, Wilkinson GR (1977) The effect of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55: 347–359
Lam FC, Hung CT, Perrier DG (1985) Estimation of variance for harmonic mean half-lives. J Pharm Sci 74: 229–231
Niazi N (1976) Volume of distribution as a function of time. J Pharm Sci 65: 452–454
Piafsky KM, Borgå O, Odar-Cederlöf I, Johansson C, Sjöqvist F (1978) Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma α1-acid glycoprotein. N Engl J Med 299: 1435–1439
Tolley DA (1984) The effect of terodiline on patients with detrusor instability. Scand J Urol Nephrol 87 [Suppl]: 51–54
Peters D and The Multicentre Study Group (1984) Terodiline in the treatment of urinary frequency and motor urge incontinence. A controlled multicentre trial. Scand J Urol Nephrol 87 [Suppl]: 21–33
Schaaf LJ, Lam FC, Perrier DG (1986) Comparison of harmonic mean versus arithmetic mean clearance values. J Pharm Sci 75: 427–429
Schmucker DL (1985) Aging and drug disposition: An update. Pharmacol Rev 37: 133–148
Verbeeck RK, Cardinal JA, Wallace SM (1984) Effect of age and sex on the plasma binding of acidic and basic drugs. Eur J Clin Pharmacol 27: 91–97
Wilkinson GR, Shand DG (1975) A physiological approach to heaptic drug clearance. Clin Pharmacol Ther 18: 377–390
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Hallén, B., Magnusson, A., Bogentoft, S. et al. Single- and multiple-dose pharmacokinetics of terodiline in geriatric patients. Eur J Clin Pharmacol 34, 291–297 (1988). https://doi.org/10.1007/BF00540958
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DOI: https://doi.org/10.1007/BF00540958