In vitro interactions between aged garlic extract and drugs used for the treatment of cardiovascular and diabetic patients.
BACKGROUND
Disease preventing effects gained by garlic consumption have been recognized since early period of history, making commercially available garlic supplements attractive to the general public. Possible pharmacokinetic interactions which could occur between applied drugs and aged garlic extract (AGE) are unknown.


OBJECTIVE
To test in vitro impact of some garlic phytochemicals on P-glycoprotein (Pgp), the most recognized efflux transporter, and the effect of AGE on passive membrane permeability, absorptive and secretory intestinal transporters.


METHODS
Rat small intestine and Caco-2 cell monolayers, mounted in side-by-side diffusion chambers were used.


RESULTS
Hydrophilic sulphur compounds increased Pgp mediated Rhodamine 123 (Rho123) efflux, whereas the lipophilic ones increased Pgp efflux through rat ileum but not through Caco-2 cell monolayers. Increased activities of secretory (Pgp, multidrug-resistance associated protein 2) and absorptive (monocarboxylate transporter 1, organic anion transporting polypeptide) transporters involved in drug absorption were observed in rat small intestine and Caco-2 cell monolayers in the presence of AGE. Transport of drugs mediated by breast cancer resistance protein and H(+)-oligopeptide transporter 1 was activated in rat intestine but inhibited through Caco-2 cells. Passive membrane permeability of tested compounds remained unaltered through rat small intestine, while significant changes were observed with Caco-2 cell monolayers.


CONCLUSIONS
Due to the observed in vitro pharmacokinetic interactions between AGE and investigated cardiovascular, antidiabetic and antiviral drugs, in vivo absorption changes are possible, but the magnitude of change depends on the most profound process involved (influx, efflux, passive diffusion) in compounds permeability.
Berginc
Katja
K
Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia. katja.berginc@ffa.uni-lj.si
Žakelj
Simon
S
Kristl
Albin
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D018938:Caco-2 Cells; D002317:Cardiovascular Agents / Q000032:analysis / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability; D019587:Dietary Supplements / Q000032:analysis; D018565:Food-Drug Interactions; D005737:Garlic / Q000737:chemistry*; D006801:Humans; D007004:Hypoglycemic Agents / Q000032:analysis / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism; D000074011:Peptide Transporter 1; D010936:Plant Extracts / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D027981:Symporters / Q000378:metabolism; D057900:Transcytosis; D000099233:Monocarboxylate Transport Protein 1
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002317:Cardiovascular Agents; D007004:Hypoglycemic Agents; D027501:Monocarboxylic Acid Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D027361:Organic Anion Transporters; D000074011:Peptide Transporter 1; D010936:Plant Extracts; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1