Sotalol pharmacokinetics

Poirier JM, Le Jeunne C, Cheymol G, Cohen A, Barre J, Hugues FC Comparison of propranolol and sotalol pharmacokinetics in obese subjects. J. Pharm. Pharmacol. 1990 42 344-348. 

Badaloni, E. et al., Enantioselective liquid chromatographic-electrospray mass spectrometric assay of fS-adrenergic blockers application to a pharmacokinetic smdy of sotalol in human plasma, J. Chromatogr. B, 796, 45, 2003. 

Sotalol is well absorbed orally with bioavailability of approximately 100%. It is not metabolized in the liver and is not bound to plasma proteins. Excretion is predominantly by the kidneys in the unchanged form with a half-life of approximately 12 hours. Because of its relatively simple pharmacokinetics, solatol exhibits few direct drug interactions. Its most significant cardiac adverse effect is an extension of its pharmacologic action a dose-related incidence of torsade de pointes that approaches 6% at the highest recommended daily dose. Patients with overt heart failure may experience further depression of left ventricular function during treatment with sotalol. 

Salazar, D., Much, D., Nichola, P., Seibold, J., Shindler, D., and Slugg, P., A pharmacokinetic-pharmacodynamic model of d-sotalol Q-Tc prolongation during intravenous administration to healthy subjects, Journal of Clinical Pharmacology, Vol. 37, No. 9, 1997, pp. 799-809. 

Berglund G, Descamps R, Thomis JA. Pharmacokinetics of sotalol after chronic administration to patients with renal insufficiency. Eur J Clin Pharmacol 1980 18(4) 321-6. 

Carr, R.A., Foster, R.T., Lewanczuk, R.Z. Hamilton, P.G. (1992) Pharmacokinetics of sotalol enantiomers in humans. Journal of Clinical Pharmacology, 32, 1105-1109. 

Eoster RT and Carr RA, Sotalol, APDS, 21, 501-533 (1992). Cited W G, which in turn cited Garrett and Schnelle, 1971 (see no. 1279). NB Hinderling PH, Schmidlin O, Seydel JK, Quantitative relationships between structure and pharmacokinetics of beta-adrenoceptor blocking agents in man, J. Pharmacokin. Biopharm., 12, 263-287 (1984). See Sotalol, no. 1279. 

Single-dose pharmacokinetic studies may provide sufficient information for dosage selection in medicinal product that exhibit linear pharmacokinetics. Medicinal products that exhibit non-linearity in absorption, distribution and elimination may require steady-state studies. Such an approach has been used to assess the pharmacokinetics of an extemporaneously prepared sotalol syrup formulation in neonates, infants, and younger and older children. Scheduled blood samples were taken over a 36-hour time interval following dose administration (Saul et al, 2001). 

The use of population pharmacokinetics and a sparse sampling approach allow each patients to contribute as few as two to four observations at predetermined times to an overall population. Use of the area under the curve (AUC) will minimise the number of samples required from each patient. Population models allow researchers to assess and quantify potential sources of variability in exposure and response in the target population. Population pharmacokinetics seeks to discover which measurable pathophysiological factors cause changes in the dose-concentration relationship and to what degree, so that the appropriate dosage can be recommended. The pharmacokinetic-pharmacodynamic approach has been used to assess sotalol syrup formulations (Shi et al, 2001). Ten blood samples were taken from... 

Saul J P, Schaffer M S, Karpawich P P, et al. (2001). Single-dose pharmacokinetics of sotalol in a pediatric population with supraventricular and/or ventricular tachyarrhythmia. / Clin Pharmacol 41 35—43. 

Singh BN, Deedwania P, Nademanee K, Ward A, Sorkin EM Sotalol A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use. Drugs 1987 34 311-349. 

Carr RA, Foster RT, Lewanczuk RZ, Hamilton PG Pharmacokinetics of sotalol enantiomers in humans. J. Clin. Pharmacol. 1992 accepted. 

Ishizaki T, Hirayama H, Tawara K, Nakaya H, Sato M, Sato K Pharmacokinetics and pharmacodynamics in young normal and elderly hypertensive subjects A study using sotalol as a model drug. J. Pharmacol. Exp. Ther. 1980 212 173-181. 

Kato, R. Ikeda, N. Yabek, S. Kannen, R. Singh, B.N. Electrophysiologic effects of the levo- and dextrorotatory isomers of sotalol in isolated cardiac muscle and their in vivo pharmacokinetics. J. Am. CoU. Cardiol. 1986, 7, 116-125. 

Advani, S.V. Singh, B.N. Pharmacodynamic, pharmacokinetic and antiar-rhythmic properties of d-sotalol, the dextro-isomer of sotalol. Drugs 1995,49, 664 19. 

The haemodynamic and pharmacokinetic effects of atenolol and metoprolol in heaithy subjects do not appear to be changed by al-cohoi. There is some evidence that alcohol modestly reduces the haemodynamic effects of propranolol, and some of the effects of sotalol may also be changed by alcohol. Some evidence suggests that the effects of alcohol and atenolol/chlortalidone or propranolol are additive on the performance of some psychomotor tests, but the importance of this is uncertain. 

The pharmacokinetics of procainamide are little changed by either propranoioi or metoprolol. Both sotalol and procamamide have QT-intervai proionging effects, which may be additive if they are used together. 

A study in 12 healthy subjects found that when sotalol 160 mg was given with hydrochlorothiazide 25 mg the pharmacokinetics of both drugs were unchanged. ... 

Sundquist H, Anttila M, Simon A, Reich JW. Comparative bioavailability and pharmacokinetics of sotalol adm blistered alone and in combination with hydrochlorothiazide. JCUn Pharmacol (1979) 19,557-64. 

Mscellaneous. A single dose of intravenous esmolol did not affect the pharmacokinetics of multiple-dose digoxin, except that a small increase was seen in the AUC of digoxin. The pharmacokinetics of multiple-dose digoxin have been shown to be unaffected by acebutolol, bevan-tolol 200 mg daily, bisoprolol 10 mg daily, nebivolol 10 mg daily, or sotalol 80 to 320 mg daily. 

Shi J, Ludden TM, Melikian AP, Gastonguay MR, Hinderling PH (2001) Population pharmacokinetics and pharmacodynamics of sotalol in pediatric patients with supraventricular or ventricular tachyarrhythmia. J Pharmacokinet Pharmacodyn 28 555-575 Shin JG, Kang WK, Shon JH, Arefayene M, Yoon YR, Kim KA, Kim DI, Kim DS, Cho KH, Woosley RL, Flockhart DA (2007) Possible interethnic differences in quinidine-induced QT prolongation between healthy Caucasian and Korean subjects. Br J Clin Pharmacol 63 206-215... 

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