title: Combined versus monotherapy or concurrent therapy for treatment of thalassaemia.
abstract: A combined deferasirox (DFX) and deferiprone (DFP) treatment protocol for relieving thalassemia patients' iron-overload was designed and the pharmacokinetic study was performed by LC-MS/MS. For this open-label, randomized trial, eight patients were recruited and randomly allocated to different treatment regimens: (A) monotherapy with single oral dose of DFX 30 mg/kg, (B) monotherapy with DFP 80 mg/kg/day, twice daily, (C) combined therapy with DFX and DFP (DFX 30 mg/kg for first dose, DFP 40 mg/kg 7 hours later, and DFP 40 mg/kg after another 7 h) and (D) concurrent therapy with DFX 30 mg/kg and DFP 80 mg/kg. Descriptive statistics evaluated pharmacokinetic parameters, AUC0-t, AUC0-inf, Cmax, Tmax, T1/2 and MRT. A positive pharmacokinetic drug interaction was observed in combined therapy. In case of DFX, combined therapy tallied about 2-fold larger than monotherapy in AUC, 1.5-fold larger in Cmax, 1 h longer in Tmax, but 1 h shorter in T1/2. Regarding DFP, most such parameters of combined therapy concurred with monotherapy. Conversely, negative drug interaction was observed in concurrent therapy. With DFX, concurrent therapy attained 1.2- to 2.2-fold lower than monotherapy in AUC0-t and Cmax, 0.6-h shorter in Tmax, and 3-fold longer in T1/2. With DFP, concurrent therapy proved approximately 2-fold larger than monotherapy in AUC and Cmax, 2.5-fold longer in T1/2, and 1.4-fold longer in MRT. Follow-up of subjects' clinical examinations and subjective symptoms showed no adverse events. Our findings showed the combined therapy had advantages, safe, convenient and painless for patients, over the existing concurrent therapy with deferoxamine (DFO) and DFX.
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. Research department, Yung Shin Pharmaceutical Ind. Co., LTD, Taiwan, R.O.C.
authors: Ta-Shu
authors: TS
authors: Song
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: Yow-Wen
authors: YW
authors: Hsieh
authors: Department of Pediatrics, Children's Hospital, China Medical University, Taichung, Taiwan, R.O.C. Department of Biotechnology, Asia University, Taichung, Taiwan, R.O.C.
authors: Ching-Tien
authors: CT
authors: Peng
authors: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan, R.O.C.
authors: Tai-Lin
authors: TL
authors: Chen
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors: Hong-Zin
authors: HZ
authors: Lee
authors: Department of Biotechnology, Asia University, Taichung, Taiwan, R.O.C. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
authors: Jing-Gung
authors: JG
authors: Chung
authors: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C. China Medical University Hospital, Taichung, Taiwan, R.O.C. mjhou@mail.cmu.edu.tw.
authors: Mann-Jen
authors: MJ
authors: Hour
mesh_terms: D000293:Adolescent; D000328:Adult; D000077543:Deferiprone; D003676:Deferoxamine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D011728:Pyridones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D013789:Thalassemia / Q000150:complications* / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine
keywords: Combined therapy; LC-MS/MS; deferasirox (DFX); deferiprone (DFP); pharmacokinetics; thalassaemia patients