B.Charpiat(1), N.Laurent(1), J.M.Sab(2), V.Breant(1), C.Ducerf(3), S.Tigaud(4), D.Robert(2), R.W.Jelliffe(5)
(1)dpt of pharmacy, (2)intensive care dpt, (3)surgery dpt, (4)microb. dpt., Croix-Rousse Hospital, Lyon, France, (5)Lab.applied pharmacokinet., USC, L.A , USA
Objective: The purpose of the present study was to estimate the variability of cyclosporine pharmacokinetic parameters (slope of volume to body weight-VS, elimination rate constant-Kel, and the other rate constants KCP, going from the serum compartment out to the peripheral compartment, and KPC, going back), in hepatic transplant patients.
Methods: These parameters were calculated from observationnal data obtained without modifying the therapeutic drug monitoring scheme usually employed i.e. one serum level measured per day. Daily data collection during the 7 post-operative days was performed for 21 patients (4F, 17M; mean age = 46±12.4 yr; mean weight 73±13 kg) from June 93 to Feb 94. Cyclosporine was administered by continuous infusion at a mean starting rate of 69.8 ± 15.4µg/kg/h. 112 whole blood levels (5.33±1.2 /patient) were measured by FPIA with monoclonal antibody. Data analysis was performed using the Nonparametric Expectation Maximisation (NPEM) algorithm, in the NPEM2 software, which computes the location and probability mass of the overall joint probability density. The iterative Bayesian population modeling first part program was used to determine the probable ranges of the parameters values.
Results: Log-likelihood value of -252.752 was achieved on the 50th cycle. Table 1 presents the mean, the mode, the median, the .25, .75 quartiles and percentage coefficient variation (%CV) identified for each variable.
| parameters | mean | mode | .25 quartiles | median | .75 quartiles | %cv |
| vs (I/kg) | 0.7602 | 0.3350 | 0.3197 | 0.4403 | 0.8023 | 101.1 |
| kel(h-1) | 0.4419 | 0.6782 | 0.2114 | 0.3556 | 0.6764 | 64.5 |
| kcp(h-1) | 0.6786 | 0.0880 | 0.1996 | 0.6782 | 1.0753 | 72.5 |
| kpc(h-1) | 0.4576 | 0.0142 | 0.0406 | 0.1307 | 1.0636 | 118.2 |
Figure 1 shows the joint probability density function using VS and Kel
The values of these parameters will be compared with those previously published. The results of this population study will be validated by using this parameter as a new population model for a Bayesian program for adaptive control on a subsequent group of patients.
Reference: PAGE 3 () Abstr 849 [www.page-meeting.org/?abstract=849]
Poster: poster