Telavancin and hydroxy propyl-beta-cyclodextrin clearance during continuous renal replacement therapy: an in vitro
Jignes H Patel1, Marianne D Churchwell, Julie D Seroogy
1University of Kentucky College of Pharmacy, Department of Pharmaceutical Sciences, Lexington, Kentucky, USA.
The International Journal of Artificial Organs
|November 28, 2009
Summary
This study investigated telavancin and HP-beta-CD clearance during continuous renal replacement therapy (CRRT). Telavancin clearance varied by filter type and flow rates, suggesting potential dosing adjustments. HP-beta-CD showed substantial clearance, possibly preventing accumulation.
Area of Science:
- Pharmacology
- Nephrology
- Biochemistry
Background:
- Telavancin, a lipoglycopeptide antimicrobial, requires hydroxy propyl-beta-cyclodextrin (HP-beta-CD) for solubility.
- Its disposition during continuous renal replacement therapies (CRRT) remains uncharacterized.
Purpose of the Study:
- To assess the transmembrane clearances (CLtm) of telavancin and HP-beta-CD during CRRT.
- To evaluate the impact of hemodiafilter type and flow rates on drug and excipient removal.
Main Methods:
- An in vitro bovine blood model was used to simulate continuous hemofiltration and hemodialysis.
- AN69 and polysulfone hemodiafilters were tested at various ultrafiltrate and dialysate flow rates (1-6 L/hr).
Main Results:
- Telavancin CLtm ranged from 0.25-0.31 during hemofiltration and was similar between filter types.
- During hemodialysis, telavancin CLtm (0.10-0.43) was higher with polysulfone filters, especially at higher flow rates.
- HP-beta-CD demonstrated substantial clearance (0.63-1.38) across CRRT modalities and flow rates.
Conclusions:
- Telavancin CRRT clearance depends on hemodiafilter type and flow rates, potentially necessitating dosage adjustments.
- Significant HP-beta-CD clearance suggests it may prevent accumulation during CRRT.
- Further in vivo pharmacokinetic studies in CRRT patients are warranted.
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