Telavancin and hydroxy propyl-beta-cyclodextrin clearance during continuous renal replacement therapy: an in vitro study.
OBJECTIVE
Telavancin is a lipoglycopeptide antimicrobial agent which has been approved in Europe and has been recently FDA approved in the United States. Telavancin's parenteral solution contains hydroxy propyl-beta -cyclodextrin (HP-beta -CD) to enhance its solubility. The disposition of telavancin and HP-beta -CD during continuous renal replacement therapies (CRRT ) has not been previously reported.


METHODS
The transmembrane clearances (CLtm ) of telavancin and HP-beta -CD during continuous hemofiltration and hemodialysis were assessed using an in vitro bovine blood model with AN69 and polysulfone hemodiafilters at varying ultrafiltrate and dialysate flow rates (1, 2, 3, & 6 l/hr).


RESULTS
The mean telavancin sieving coefficient ranged from 0.25 to 0.31 during continuous hemofiltration. At all ultrafiltration rates, no differences were observed in telavancin CLtm between the two hemodiafilter types. For continuous hemodialysis, mean telavancin saturation coefficients ranged from 0.10 to 0.43 and CLtm tended to be higher for the polysulfone hemodiafilter than the AN69 hemodiafilter, especially at higher flow rates. Mean HP-beta -CD sieving coefficients ranged from 0.63 to 1.03 and saturation coefficients from 0.63 to 1.38, resulting in a CLtm that was similar to ultrafiltrate and dialysate flow rates.


CONCLUSIONS
Telavancin CLtm is dependent on hemodiafilter type, dialysate and ultrafiltration rates. CRRT with high ultrafiltrate or dialysate rates may result in sufficient telavancin clearance to alter telavancin dosing. HP-beta -CD clearance by continuous hemodialysis or continuous hemofiltration is substantial and may be sufficient to prevent HP-beta -CD accumulation in subjects receiving CRRT . Pharmacokinetic studies conducted in patients receiving CRRT and telavancin are needed to confirm these in vitro findings.
Patel
Jignes H
JH
University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences, Lexington, Kentucky, USA.
Churchwell
Marianne D
MD
Seroogy
Julie D
JD
Barriere
Steven L
SL
Grio
Maricor
M
Mueller
Bruce
B
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000180:Acrylic Resins / Q000737:chemistry; D000181:Acrylonitrile / Q000031:analogs & derivatives / Q000737:chemistry; D000617:Aminoglycosides / Q000097:blood*; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood*; D002417:Cattle; D005079:Excipients / Q000378:metabolism*; D006440:Hemofiltration / Q000295:instrumentation; D007700:Kinetics; D000077427:Lipoglycopeptides; D008567:Membranes, Artificial; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D006435:Renal Dialysis / Q000295:instrumentation; D013450:Sulfones / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000097:blood*
D000180:Acrylic Resins; D000617:Aminoglycosides; D000890:Anti-Infective Agents; D005079:Excipients; D000077427:Lipoglycopeptides; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C017662:polysulfone P 1700; C016892:AN-69; D000181:Acrylonitrile; C487637:telavancin