PMID- 23150468
OWN - NLM
STAT- MEDLINE
DCOM- 20130521
LR  - 20151119
IS  - 1520-6017 (Electronic)
IS  - 0022-3549 (Linking)
VI  - 102
IP  - 1
DP  - 2013 Jan
TI  - Biocompatible microemulsion modifies the pharmacokinetic profile and 
      cardiotoxicity of doxorubicin.
PG  - 289-96
LID - 10.1002/jps.23368 [doi]
AB  - Doxorubicin (DOX) is an anthracycline antibiotic with a broad antitumor spectrum. 
      However, the clinical use of DOX is limited because of its cardiotoxicity, a 
      dose-dependent effect. Colloidal drug delivery systems, such as microemulsions 
      (MEs), allow the incorporation of drugs, modifying the pharmacokinetic (PK) 
      profile and toxic effects. In this study, we evaluated the PK profile and 
      cardiotoxicity of a new DOX ME (DOX-ME). The PK profile of DOX-ME was determined 
      and compared with that of the conventional DOX after single-dose administration 
      (6 mg/kg, intravenous) in male Wistar rats (n = 12 per group). The cardiotoxicity 
      of DOX formulations was evaluated by serum creatine kinase MB (CKMB) activity in 
      both animal groups before and after drug administration. The plasma DOX 
      measurements were performed by high-performance liquid chromatography with 
      fluorescence detection, and the CKMB levels were assayed using the CKMB Labtest(R) 
      kit. The ME system showed a significant increase in plasma DOX concentrations and 
      lower distribution volume when compared with conventional DOX. Serum CKMB 
      activity increased after conventional DOX administration but was unchanged in the 
      DOX-ME group. These results demonstrate modifications in drug access to 
      susceptible sites using DOX-ME. DOX-ME displayed features that make it a 
      promising system for future therapeutic application.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Assumpcao, Juliana Uruguay Correa Vidigal
AU  - Assumpcao JU
AD  - School of Pharmaceutical Sciences, Sao Paulo State University, UNESP, Araraquara 
      14801-902, SP, Brazil.
FAU - Campos, Michel Leandro
AU  - Campos ML
FAU - Ferraz Nogueira Filho, Marco Antonio
AU  - Ferraz Nogueira Filho MA
FAU - Pestana, Kelly Chrystina
AU  - Pestana KC
FAU - Baldan, Helen Mariana
AU  - Baldan HM
FAU - Formariz Pilon, Thalita Pedroni
AU  - Formariz Pilon TP
FAU - de Oliveira, Anselmoc Gomes
AU  - de Oliveira AG
FAU - Peccinini, Rosangela Goncalves
AU  - Peccinini RG
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121113
PL  - United States
TA  - J Pharm Sci
JT  - Journal of pharmaceutical sciences
JID - 2985195R
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Biomarkers)
RN  - 0 (Emulsions)
RN  - 0 (Lipids)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.7.3.2 (Creatine Kinase, MB Form)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/administration & 
      dosage/blood/chemistry/*pharmacokinetics/*toxicity
MH  - Biomarkers/blood
MH  - Chemistry, Pharmaceutical
MH  - Chromatography, High Pressure Liquid
MH  - Creatine Kinase, MB Form/blood
MH  - Doxorubicin/administration & dosage/blood/chemistry/*pharmacokinetics/*toxicity
MH  - Emulsions
MH  - Heart Diseases/blood/chemically induced/*prevention & control
MH  - Injections, Intravenous
MH  - Lipids/chemistry
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Technology, Pharmaceutical/methods
EDAT- 2012/11/15 06:00
MHDA- 2013/05/23 06:00
CRDT- 2012/11/15 06:00
PHST- 2012/08/17 00:00 [received]
PHST- 2012/09/22 00:00 [revised]
PHST- 2012/10/19 00:00 [accepted]
PHST- 2012/11/15 06:00 [entrez]
PHST- 2012/11/15 06:00 [pubmed]
PHST- 2013/05/23 06:00 [medline]
AID - S0022-3549(15)31283-1 [pii]
AID - 10.1002/jps.23368 [doi]
PST - ppublish
SO  - J Pharm Sci. 2013 Jan;102(1):289-96. doi: 10.1002/jps.23368. Epub 2012 Nov 13.