Clearance of quinupristin-dalfopristin (Synercid) and their main metabolites during continuous veno-venous hemofiltration (CVVH) with or without dialysis.
BACKGROUND
Quinupristin-dalfopristin (Q/D) is often utilized in critically ill patients, some of whom require CVVH. This study was undertaken to determine the clearance of O/D and their main active metabolites (RPR 100391, RP 69012, RP 12536) via CVVH in the swine model.


METHODS
Q/D 7.5 mg/kg was intravenously administered over 0.5 h to 12 swine after induction of acute renal failure by ligation of the renal arteries. At 0.5 h post injection, the CVVH procedure was initiated and continued for 8 hours at the following pump rates: (1)100 mL/min, (2)180 rnL/min, and (3)100 mL/min with dialysis (flow rate: 1 L/h). Blood and ultrafiltrate samples were collected at 1 h intervals and assessed by a validated HPLC method.


RESULTS
Plasma analysis suggests rapid metabolism to the main active metabolites which are appreciably cleared as demonstrated by high clearance and sieving coefficient estimates. Mean clearance estimates for RP 69012, RP 100391, and RP 12536 are 729, 777, and 578 mL/h in the 100 mL/min CVVH group, 772, 785, 685 mL/min in the 180 mL/min CVVH group, and 753, 791, 616 mL/min in the 100 mL/min CVVH group with 1 L/h dialysis, respectively.


CONCLUSIONS
These data reveal that Q/D is rapidly metabolized and the metabolites are cleared to a large extent via CVVH. Due to the considerable contribution of the metabolites to overall in vivo activities, additional studies are required to fully quantify their removal before final dosage modifications for patients undergoing CVVH can be recommended.
Kim
M K
MK
Department of Pharmacy Research, Hartford Hospital, CT 06102-5037, USA.
Banevicius
M A
MA
Zhong
M
M
Shi
X
X
Hu
M
M
Nightingale
C H
CH
Nicolau
D P
DP
D000818:Animals; D004359:Drug Therapy, Combination / Q000378:metabolism / Q000493:pharmacokinetics*; D017583:Hemodiafiltration / Q000379:methods*; D006440:Hemofiltration / Q000379:methods*; D023421:Models, Animal; D013552:Swine; D014769:Virginiamycin / Q000378:metabolism / Q000493:pharmacokinetics*
D014769:Virginiamycin; C062940:quinupristin-dalfopristin