649. Pharmacokinetics (PK) of Colistin Methanesulfonate (CMS) and Formed Colistin in End-Stage Renal Disease (ESRD) Patients Receiving Chronic Hemodialysis (HD)
Session: Poster Abstract Session: Pharmacokinetics and Adverse Drug Reactions
Friday, October 21, 2011
Room: Poster Hall B1
Background: 

Emergence of multidrug-resistant (MDR) gram-negative bacteria (GNB) has led to resurgence of colistin for therapy of MDR GNB infections. Data on PK of CMS and colistin, and appropriate dosage regimens of CMS for ESRD patients receiving chronic HD are limited. The aim of the study was to determine PK of CMS and colistin in ESRD patients receiving chronic HD.

Methods: 

10 ESRD patients (8 male, median age 54 y, and median body weight 71 Kg) receiving adequate regular 4-h HD session 3 times a week were enrolled. A single dose of CMS (150 mg colistin base activity, CBA) was infused IV over 30 min. Serial blood samples from peripheral vein (pre and 0.5, 1, 2, 4, 6, 8, 12, 24 and 48 h post-start CMS infusion) were collected. HD was commenced 1 h after CMS infusion. Serial blood samples from arterial side and venous side of HD catheter were collected at 0.5, 1.5 and 2.5 h after commencing HD. Hemodialysate samples were collected at 0.5, 1.5, 2.5 and 3.5 h after commencing HD. 24-h urine samples were also collected. CMS and colistin concentrations in plasma, hemodialysate and urine were quantified by HPLC. PK analysis was conducted using WinNonlin.  

Results: 

Two-compartmental model was fitted for CMS PK in plasma (R2=0.98), and one-compartmental model for colistin PK in plasma (R2=0.94). The mean (SD) predicted PK parameters and AUC0-24 of CMS and colistin in plasma are shown below.  

 

 

Appar Vd

(L)

Appar CL (L/h)

Cmax (mg/L)

Tmax

(h)

T1/2

(h)

AUC0-24

(h.mg/L)

CMS

43.3 (27.0 )

5.4 (0.4)

29.8 (21.0)

--

11.3 (5.9)

79.0 (11.5)

Colistin

183.0 (62.0)

4.4 (1.2)

0.7 (0.2)

8.3 (3.1)

31.6 (8.6)

14.8 (3.3)

 Conclusion: 

Colistin clearance in ESRD patients receiving chronic HD was high resulting in low plasma colistin concentrations for entire 24 h and small AUC0-24 after administration of 150 mg CBA. The predicted PK parameters are useful for determining CMS dosage regimen if the ESRD patients receiving chronic HD require CMS therapy.


Subject Category: A. Antimicrobial agents and Resistance

Pornpan Koomanachai, MD1, Gong Chen, PhD2, Hee Ji Lee, PhD2, Jovan Jacob, M Pharm Chem2, Anupop Jitmuang, MD1, Somkiat Wasuwattakul, MD1, Suchai Sritippayawan, MD1, Jian Li, PhD2, Roger L. Nation, PhD2 and Visanu Thamlikitkul, MD1, (1)Mahidol University, Bangkok, Thailand, (2)Monash University, Melbourne, Australia

Disclosures:

P. Koomanachai, None

G. Chen, None

H. J. Lee, None

J. Jacob, None

A. Jitmuang, None

S. Wasuwattakul, None

S. Sritippayawan, None

J. Li, None

R. L. Nation, None

V. Thamlikitkul, None

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