title: Plasma pharmacokinetics and gastrointestinal transit of a new propionyl-L-carnitine controlled release formulation.
abstract: Propionyl-L-carnitine is a naturally occurring analogue of L-carnitine (LC) produced in the body. PLC administration has shown beneficial effects in cardiovascular pathologies. In ulcerative colitis (UC), oral PLC treatment increased clinical presentation and positively influenced colon histology. In the present study, the MMX Multi Matrix System® (MMX™) was used as drug delivery strategy for targeted PLC colon delivery. A pharmacoscintigraphic study (n = 6 healthy volunteers) described release characteristics of two MMX-PLC-HCl controlled release 500 mg tablets. A pharmacokinetic (PK) parallel group study (n = 24) determined safety, plasma PLC concentrations and PK parameters after single and multiple doses. Gastrointestinal transit was slow and variable. The colon was the main site of PLC release and absorption. After single 500 or 1000 mg PLC doses plasma PLC and LC increased up to 2.6 and 1.2-1.3-fold compared to baseline. Multiple doses of 500 and 1000 mg twice a day over 7 days did not significantly increase maximum plasma concentrations of PLC or LC with respect to concentrations achieved after single dose administration. The colon is the main site of PLC release and absorption from MMX-PLC tablets. A daily dose of 500 mg to 1000 mg PLC twice a day was well tolerated, justifying further studies in patients with pathologies of the distal gastrointestinal tract to evaluate the efficacy of the MMX-PLC formulation.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Wagner
authors.forename: Antonio
authors.initials: A
authors.lastname: Rusca
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Manfred
authors.initials: M
authors.lastname: Tschurlovits
authors.forename: Silvia
authors.initials: S
authors.lastname: Pace
authors.forename: Antonio
authors.initials: A
authors.lastname: Longo
authors.forename: Massimo
authors.initials: M
authors.lastname: Pedrani
authors.forename: Roberto
authors.initials: R
authors.lastname: Villa
authors.forename: Enrico
authors.initials: E
authors.lastname: Frimonti
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002331:Carnitine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005772:Gastrointestinal Transit / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011877:Radionuclide Imaging; D013997:Time Factors; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; C003223:propionylcarnitine; D002331:Carnitine