Dose proportionality of once-daily trazodone extended-release caplets under fasting conditions.

An extended-release trazodone HCl formulation, Trazodone Contramid OAD (TzCOAD), was developed as scored 150-mg and 300-mg caplets for once-daily administration. Dose proportionality of intact and bisected caplets (dose range, 75-375 mg) was evaluated in a single-dose, randomized, 5-way crossover study. Plasma trazodone and m-chlorophenylpiperazine (mCPP) levels were determined using a validated liquid chromatography-tandem mass spectroscopy method. Dose proportionality was assessed based on confidence intervals for logarithmically transformed, dose-normalized maximum plasma concentration (C(max)), area under the plasma concentration versus time data pairs (AUC(0-t)), and area under the curve from time 0 to infinity (AUC(0-∞)) in relation to the acceptance range of 80% to 125% (bioequivalence approach). The power method, combined with confidence interval criteria, was also used to assess proportionality. The conclusion of dose proportionality was generally supported using the bioequivalence approach. Based on the power model, values of the slope and corresponding 90% confidence interval for trazodone C(max), AUC(0-t), and AUC(0-∞) were 0.948 (0.899-0.997), 0.920 (0.875-0.964), and 0.913 (0.867-0.958), respectively. All were within the acceptance interval (0.861-1.139). Results for mCPP also fell within the acceptance interval. TzCOAD exhibits linear pharmacokinetics over doses ranging from 75 to 375 mg and maintains its controlled-release properties when the caplets are bisected along the score line.

Effect of an oral iron(III)-hydroxide polymaltose complex on tetracycline pharmacokinetics in patients with iron deficiency anemia.

The study was carried out as an open-label, but laboratory-blind, single-dose, single-centre, randomized, two-period crossover study. Twenty-two patients with iron deficiency anemia completed the study. The study consisted of two treatment phases of 36 h, separated by a washout period of between 6 and 14 days. The two treatments were given orally. The reference treatment was tetracycline (CAS 60-54-8) alone (2 x 250 mg capsules) and the test treatment was iron(III)-hydroxide polymaltose complex (IPC, Maltofer) together with tetracycline (2 x 250 mg capsules). IPC had no pharmacokinetic effect on the rate of absorption of tetracycline. With concomitant administration of tetracycline and IPC sufficiently high tetracycline concentrations, to ensure bacteriostasis, will be reached. An inhibitor effect of IPC to the tetracycline absorption, as it is known for ferrous salts, could not be observed.

Effect of oral aluminium hydroxide on iron absorption from iron(III)-hydroxide polymaltose complex in patients with iron deficiency anemia / a single-centre randomized controlled isotope study.

The study was carried out as an open-label, laboratory-blind, single-dose, randomized, two-period crossover, isotope efficacy study. Twenty-two patients with iron-deficiency anemia were enrolled in the study. The study consisted of two treatment phases of 15 days each, including blood sample measurements for Fe-59 activity. The 2 treatments were given orally. Treatment A was Fe-59 labeled iron(III)-hydroxide polymaltose complex (IPC, Maltofer), equivalent to 100 mg elemental iron given orally, and Treatment B consisted of Treatment A combined with 600 mg aluminium hydroxide (CAS 21645-51-2) (10 ml). No differences between the two treatment groups with regard to the erythrocyte uptake were found, and thus IPC can be used with aluminium hydroxide, if necessary.

Effect of oral tetracycline on iron absorption from iron(III)-hydroxide polymaltose complex in patients with iron deficiency anemia / a single-centre randomized controlled isotope study.

The study was carried out as an open-label, laboratory-blind, single-dose, randomized, two-period crossover, isotope efficacy study. Twenty-two patients with iron-deficiency anemia were enrolled in the study. The study consisted of two treatment phases of 15 days each, including blood sample measurements for Fe-59 activity. The two treatments were given orally. Treatment A was Fe-59 labeled iron(III)-hydroxide polymaltose complex (IPC, Maltofer) equivalent to 100 mg elemental iron given orally. Treatment B consisted of Fe-59 labeled IPC complex equivalent to 100 mg elemental iron and 500 mg tetracycline HCl (CAS 64-75-5) given orally. No differences between the two treatment groups with regard to the erythrocyte iron uptake were found, and thus IPC can be used with tetracycline, if necessary.