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No covariates were statistically significant for the clearance of phenobarbital. At weight of 1 kg volume of distribution was 0.91 L and for every additional kg it increased in 0.91 L. The current release (1.2) supports models fitted with Monolix versions 2016 and later, NONMEM version 7.2 and later and nlmixr. NONMEM 7 up to the current version 7.2.0 is the property of ICON Development Solutions.
#Current nonmem version license#
Weight was found to be the only statistically significant covariate for the volume of distribution. NONMEM versions up through VI are the property of the Regents of the University of California, but ICON Development Solutions has exclusive rights to license their use. Severe asphyxia was defined as pH of arterial umbilical cord blood ≤7.1 and Apgar 5 ≤5, and severe HIE was defined as time to normalization of amplitude-integrated electroencephalography (aEEG) >24 h. Also like NONMEM, c(est) does not specify a lower bound, and is equivalent to specifying the parameter without Rs c function. Pirana works with R speaks NLME, NONMEM, R, Perl Speaks NONMEM (PSN). Age, body weight, sex, concomitant medications, kidney and liver function markers, as well as severity parameters of asphyxia and HIE were tested as potential covariates of pharmacokinetics of phenobarbital. This version supports NONMEM 7.2 and 7.3 with both Intel Fortran and gfortran using additional gf.xml scripts in the installation directories. Built-in support for version control and audit trails. NONMEM version 7.2® was used for the data analysis. 120 plasma sample were available from 50 newborns, median (IQR) weight 3.3 (2.8-3.5) kg and gestational age 39 (39-40) weeks. Off-diagonal OMEGA/SIGMA is rounded off to 0 as before if very small absolute value.
#Current nonmem version trial#
Included newborns received phenobarbital (the TOBY trial protocol). Now for NONMEM 6, for THETAS and diagonal OMEGA/SIGMA values x, where 0 x 0.000001, x is replaced with 0.000001 (smallest positive non-zero number that NONMEM 6 will accept) and values x, where -0.00001 x 0, are replaced with -0.00001 (largest negative non-zero number NONMEM 6 will accept). The current study uses a population modeling approach to evaluate and quantify the impact of severity of asphyxia and hypoxic-ischemic encephalopathy (HIE) on the pharmacokinetics of phenobarbital in asphyxiated newborns treated with therapeutic hypothermia.