Active Ingredient: Gabapentin
P decided that she would prefer to continue on this medication during the course of her pregnancy.
The discussion regarding the use of gabapentin was more complicated. Without it, Ms. P reported difficulty falling asleep and worse anxiety.
We calibrated this approach using tobramycin standards and accounted for dilution and matrix effects via standard spiking; we provide a full description in the Materials and Methods section.
But because E-AB measurements are far more frequent, they produce much more precise pharmacokinetic parameter estimates.
Specifically, while the cumbersome nature of blood draws and the limited amount of blood we can remove from a rat without causing undue harm limited our ex-vivo measurements to just 7 time points, the 7 s measurement frequency of E-AB measurements leads to many hundreds of data points collected per pharmacokinetic profile Figures 1 D, E.
The unprecedented precision of E-AB-derived pharmacokinetic measurements provides an opportunity for new insights into pharmacokinetic variability. In addition to studying tobramycin pharmacokinetics following IM injections, we also explored IV injections, which are the standard of care for patients receiving aminoglycoside therapy Loewenthal and Dobson,.
We did so over 1-min injection duration in a total of 17 rats 12 representative measurements are shown in Figure 2 A. Here, again, we calculated pharmacokinetic variability by performing a least-squares fit of each profile, except this time we employed a two compartment open pharmacokinetic model of a bolus injection Loftsson,.
Since drug elimination depends strongly on the overall metabolic rate of each subject at the time of measurement, this parameter has a strong influence in the bioavailability of the drug.
Error bars indicate the standard error determined by performing a least-squares fit of the drug profiles to a two-compartment pharmacokinetic model.
The high-precision measurements provided by E-AB sensors highlight the poor precision of existing predictors of tobramycin pharmacokinetics.
Discussion Here we have explored the use of E-AB sensors as a means of easily and rapidly obtaining the pharmacokinetic profiles of individuals with unprecedented precision, using the disposition kinetics of tobramycin in Sprague-Dawley rats as our model system.
Comparison with ex-vivo measurements performed using gold-standard HPLC-MS highlights both the accuracy of E-AB sensors and the pharmacokinetic precision provided by their far greater temporal resolution. The vastly improved precision of this approach renders it easy to identify significant subject-to-subject variability in drug levels following BSA-adjusted dosing, an approach long considered the gold standard for dosing tobramycin.
These results confirm the empirically known inaccuracy of BSA, or body-based approaches in general, as metrics for dose determination in this class of drugs Horrevorts et al.
Early abstinence is associated with activation of brain stress systems in the extended amygdala.
It is believed to act by blocking a specific alpha-2 d subunit of the voltage-gated calcium channel at selective presynaptic sites and, as a result, to indirectly modulate gamma butyric acid GABA neurotransmission.
We hypothesized that gabapentin would be associated with significant linear dose-related increases in rates of sustained abstinence and no heavy drinking, and decreases in abstinence-related symptoms involving sleep, mood, and craving, over the 12-week treatment course.
Our study physicians also practice internal and hospital medicine at the adjacent Scripps Green Hospital and Clinics; these facilities provide a broad range of medical services to the greater community of San Diego.
This study lacks sufficient data to meaningfully assess the reproductive safety of gabapentin.