title: Drug interaction of spirapril hydrochloride monohydrate and hydrochlorothiazide. A clinical study to compare the pharmacokinetics after administration of spirapril hydrochloride monohydrate tablets, hydrochlorothiazide tablets and fixed combination bi-layer tablets.
abstract: The potential influence of concomitantly administered hydrochlorothiazide (CAS 58-93-5) on the pharmacokinetics of spirapril (CAS 94841-17-5)/spiraprilat (CAS 83602-05-5) and of concomitantly administered spirapril on the pharmacokinetics of hydrochlorothiazide was investigated in an open, randomised, 3-way crossover study in 12 healthy male subjects. The test drug was a newly developed bi-layer tablet containing a fixed combination of spirapril hydrochloride monohydrate and hydrochlorothiazide (Quadroplus). The reference formulations were tablets containing solely spirapril hydrochloride monohydrate (Quadropril) or hydrochlorothiazide (produced exclusively for study medication). For spirapril, spiraprilat and hydrochlorothiazide the 90% confidence intervals of the AUC(0-infinity) as a measure for the extent of absorption were entirely included within the equivalence range of 0.8 to 1.25 and the 90% confidence intervals of the Cmax as a measure for the rate of absorption were entirely included within the extended equivalence range of 0.7 to 1.43. Therefore, bioequivalence was concluded for the test and reference formulations. The results suggest that hydrochlorothiazide does not interact in the fixed combination with the pharmacokinetics of spirapril and vice versa.
authors.affiliation: LAFAA Laboratory for Contract Research in Clinical Pharmacology and Biopharmaceutical Analytics GmbH, Bad Schwartau, Germany. lafaa_gmbh@t-online.de
authors.forename: Michael
authors.initials: M
authors.lastname: Schürer
authors.forename: Katharina
authors.initials: K
authors.lastname: Erb
authors.forename: Klaus
authors.initials: K
authors.lastname: Junge
authors.forename: Harald F
authors.initials: HF
authors.lastname: Schäfer
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schulz
authors.forename: Stefan
authors.initials: S
authors.lastname: Amschler
authors.forename: Sabine
authors.initials: S
authors.lastname: Krupp
authors.forename: Robert
authors.initials: R
authors.lastname: Hermann
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D004232:Diuretics; D004338:Drug Combinations; D004347:Drug Interactions; D004656:Enalapril / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D016037:Single-Blind Method; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013607:Tablets
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D004338:Drug Combinations; D049993:Sodium Chloride Symporter Inhibitors; D013607:Tablets; D006852:Hydrochlorothiazide; D004656:Enalapril; C052555:spirapril