The polymorphism of multi-drug resistance 1 gene (MDR1) does not influence the pharmacokinetics of dexamethasone loaded into autologous erythrocytes of patients with inflammatory bowel disease.
BACKGROUND
We have recently demonstrated that low doses of Dexamethasone 21-P (Dex 21-P), loaded in autologous erythrocytes and administered at monthly intervals, have been able to maintain steroid-dependent patients with Crohn's disease (CD) and ulcerative colitis (UC) in clinical remission with a progressive and complete tapering of systemic steroids.


OBJECTIVE
Since multi-drug resistance 1 gene (MDR1) has a potential influence on Dexamethasone (Dex) bioavailability, we designed this study to investigate the correlation between MDR1 genotype and Dex pharmacokinetic after its delivery in patients with inflammatory bowel disease (IBD).


METHODS
Seventeen steroid-dependent consecutive patients with IBD (10 UC mean age 36 +/- 12, and 7 Crohn's disease mean age 31 +/- 5) were consecutively recruited. The C3435T polymorphism of MDR1 gene was studied by Denaturing High Performance Liquid Chromatography (DHPLC). Serum level of Dex were determined at the end of the infusion and after 15 days by high performance liquid chromatography electrospray mass spectrometry.


RESULTS
The mean dose of Dex 21-P administered was 9.9 mg +/- 4 (range 2.7-20.3), while the mean levels of Dex at the end of the infusion and after 15 days were 0.66 +/- 0.23 mM and 0.06 +/- 0.06 mM, respectively. Concerning the C3435T genotype, two patients were wild-type, eleven heterozygotes, and four homozygotes. No correlation between basal or 15-days plasma level of Dex and MDR1 genotype was found (r = 0.19 and r = 0.21, respectively).


CONCLUSIONS
Our findings demonstrated that Dex plasma level, after infusion of autologous erythrocytes loaded with Dex 21-P are completely independent by the MDR 1 gene polymorphism. This could be another potential advantage of this modality of drug delivering.
Dipartimento di Medicina Generale e Specialistica, Unità di Gastroenterologia, Ospedale Casa Sollievo della Sofferenza Hospital, I.R.C.C.S., San Giovanni Rotondo, Italy.
V
V
Annese
A
A
Latiano
L
L
Rossi
F
F
Bossa
G
G
Damonte
B
B
Dallapiccola
S
S
Serafini
F
F
Pierigé
A
A
Andriulli
M
M
Magnani
D000328:Adult; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004337:Drug Carriers; D004912:Erythrocytes; D005260:Female; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*
D004337:Drug Carriers; D011355:Prodrugs; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone