PMID- 21277965
OWN - NLM
STAT- MEDLINE
DCOM- 20110627
LR  - 20131121
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 407
IP  - 1-2
DP  - 2011 Apr 4
TI  - Incidence of low bioavailability of leuprolide acetate after percutaneous 
      administration to rats by dissolving microneedles.
PG  - 126-31
LID - 10.1016/j.ijpharm.2011.01.039 [doi]
AB  - Two-layered dissolving microneedles of which acral portion contained leuprolide 
      acetate (LA) as solid dispersion were prepared with sodium chondroitin sulfate as 
      the base and the systemic absorption efficiency of LA was studied in rats after 
      administration to their abdominal skin. A patch contained 100 dissolving 
      microneedles of which length and basement diameter were 469.8+/-4.7 mum and 
      284.5+/-9.8 mum, where LA content was 14.3+/-1.6 mug. In vitro dissolution experiment 
      showed that LA was released from dissolving microneedle patch within 3 min. LA 
      was stable in the patch, % recoveries for 3 months were 102.2+/-1.9-95.3+/-1.9%. One 
      and half-patch of LA dissolving microneedles were administered to the rat skin 
      and plasma LA concentrations were measured by LC-MS/MS. Plasma LA concentrations 
      increased immediately after administration, and reached to the maximum level at 
      15 min, where C(max) were 6.0+/-0.7 and 16.4+/-0.9 mug/ml, respectively. The AUC were 
      5.8+/-0.8 and 14.5+/-0.4 mug h/ml and BA were 33.8+/-4.3% and 31.7+/-0.8%. When LA 
      solution was subcutaneously (s.c.) injected to rats, 50 mug/kg, the BA was 
      32.0+/-2.1%. Relative BA of LA from dissolving microneedles against s.c. solution 
      was 105.6+/-13.5%. The degradation rate of LA in the rat skin tissue homogenate was 
      very fast where the half-life was 16.3+/-5.7 min. The degradation of LA in the skin 
      tissue was the cause of the low BA of LA after percutaneous administration to 
      rats.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Ito, Yukako
AU  - Ito Y
AD  - Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, 
      Kyoto, 607-8412, Japan. yukako@mb.kyoto-phu.ac.jp
FAU - Murano, Hiroshi
AU  - Murano H
FAU - Hamasaki, Noriyuki
AU  - Hamasaki N
FAU - Fukushima, Keizo
AU  - Fukushima K
FAU - Takada, Kanji
AU  - Takada K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110126
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Antineoplastic Agents, Hormonal)
RN  - 9007-28-7 (Chondroitin Sulfates)
RN  - EFY6W0M8TG (Leuprolide)
SB  - IM
MH  - Administration, Cutaneous
MH  - Animals
MH  - Antineoplastic Agents, Hormonal/administration & dosage/*pharmacokinetics
MH  - Area Under Curve
MH  - Biological Availability
MH  - Chondroitin Sulfates/*chemistry
MH  - Chromatography, Liquid
MH  - Half-Life
MH  - Incidence
MH  - Leuprolide/administration & dosage/*pharmacokinetics
MH  - Male
MH  - Needles
MH  - Rats
MH  - Rats, Wistar
MH  - *Skin Absorption
MH  - Tandem Mass Spectrometry
MH  - Time Factors
EDAT- 2011/02/01 06:00
MHDA- 2011/06/28 06:00
CRDT- 2011/02/01 06:00
PHST- 2010/08/05 00:00 [received]
PHST- 2011/01/19 00:00 [revised]
PHST- 2011/01/21 00:00 [accepted]
PHST- 2011/02/01 06:00 [entrez]
PHST- 2011/02/01 06:00 [pubmed]
PHST- 2011/06/28 06:00 [medline]
AID - S0378-5173(11)00070-6 [pii]
AID - 10.1016/j.ijpharm.2011.01.039 [doi]
PST - ppublish
SO  - Int J Pharm. 2011 Apr 4;407(1-2):126-31. doi: 10.1016/j.ijpharm.2011.01.039. Epub 
      2011 Jan 26.