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- W2018444329 abstract "The disposition of the pharmacologically active 4-hydroxypropranolol (HO-P), its glucuronic acid conjugate (HO-P-G), and propranolol were compared after single intravenous and oral doses of propranolol in 6 normal subjects and after long-term therapy in 32 patients with hypertension or coronary artery disease. The areas under the plasma concentration/time curves (AUCoo, ng . hr/ml) after 4-mg intravenous doses of propranolol were 6.6 +/- 2.2 (mean +/- SEM) for HO-P and 55 +/- 11 for propranolol. After 20- and 80-mg oral doses the AUCoo for HO-P were 59 +/- 9 and 162 +/- 21 and for propranolol were 72 +/- 9 and 306 +/- 46. Peak HO-P concentrations were reached at 1 to 1.5 hr after the oral doses. Although there was a rapid decline in plasma HO-P between 1.5 and 3 hr when HO-P-G was still rising to levels above HO-P levels 3.5- to 5-fold, the apparent half-lifes (t1/2s) after 3 hr were in the same range for HO-P, HO-P-G, and propranolol (3.0 to 4.2 hr). While during long-term therapy plasma HO-P rose over the whole dose range (40 to 960 mg daily) in an apparently linear fashion, the HO-P/propranol plasma level ratio fell from 1.07 +/- 0.13 at 40 mg daily to only 0.09 +/- 0.01 at 640 mg daily. Plasma HO-P-G rose exponentially with dose and demonstrated significant cumulation. HO-P and HO-P-G in urine accounted for about 9% of long-term propranolol doses. This study suggests a significant contribution of HO-P to pharmacologic effects, in particular at low single and long-term oral doses of propranolol and saturation of naphthalene ring oxidation as a main determinant of propranolol bioavailability." @default.
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- W2018444329 date "1980-01-01" @default.
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- W2018444329 title "4-Hydroxypropranolol and its glucuronide after single and long-term doses of propranolol" @default.
- W2018444329 doi "https://doi.org/10.1038/clpt.1980.4" @default.
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