Co-administration of morphine with oral gabapentin has been shown to increase plasma gabapentin concentrations.
Both, Gabapentin
Enacarbil and Morphine are analgesics used to treat the post herpetic pain.
Monotherapy and combination therapy are well described in this article with the
concepts of bioequivalence studies i.e., AUC and Cmax.
Co-administration of morphine with oral
gabapentin has been shown to increase plasma gabapentin concentrations. This
study evaluated whether there was any interaction between gabapentin enacarbil
(GEn), which is a prodrug of gabapentin, and morphine in terms of
pharmacokinetics, pharmacodynamics, safety, and tolerability.
This randomized,
double-blind, 3-treatment crossover study included nonelderly, healthy male
subjects. The study subjects received (in random order and with a minimum 7-day
washout between treatments) the following: morphine placebo + GEn 600 mg;
morphine 60 mg + GEn 600 mg; and morphine 60 mg + GEn placebo.
Morphine/morphine placebo was administered in fasted conditions, and GEn/GEn
placebo was administered 2 hours later with food. The primary end points were
AUC and Cmax for gabapentin, morphine, and morphine-6-glucuronide. Pharmacodynamic
measures were limited to subject assessment of somnolence, dizziness, and
nausea conducted by using a visual analog scale (VAS). Safety monitoring
included adverse event reporting, clinical laboratory tests, vital signs, pulse
oximetry, and 12-lead ECGs.
Of the 18
enrolled subjects (mean age, 36 years), 15 (83%) completed the study. Sixteen
received GEn, 15 received morphine, and 18 received the combination. Compared
with the single treatments, the 90% CIs for the ratio of the geometric means
for both AUC and Cmax were all within 0.8 to 1.25, the accepted range for
bioequivalence. Ratios of geometric mean (90% CIs) values were as follows:
gabapentin, AUC of 1.10 (1.035–1.162) and Cmax of 1.02 (0.920–1.126); morphine,
AUC of 1.06 (1.014–1.098) and Cmax of 1.05 (0.967–1.134); and
morphine-6-glucuronide, AUC of 0.992 (0.929–1.058) and Cmax of 0.953
(0.855–1.062). Mean changes from predose VAS scores were generally small and
suggested a slight increase in dizziness after GEn and slight increases in
dizziness, somnolence, and nausea after morphine. Trends were noted suggesting
slightly greater score changes from predose with the combination treatment than
with either drug given alone for somnolence and dizziness. Adverse events were
generally mild; there were no serious adverse events or subject withdrawals due
to adverse events. Headache and nausea were among the most commonly reported
events for the combination and morphine treatments (headache, 27% and 28%;
nausea, 13% and 11%, respectively). There were fewer adverse events with GEn
alone than with either of the combination regimens.
No significant
pharmacokinetic interaction between the 2 drugs was seen in this study. The VAS
data suggest that the potential exists for increased adverse effects when GEn
and morphine are co-administered.
Clin Ther. 2015 Feb 1;37(2):349-57
Gabapentin Enacarbil and Morphine Administered in Combination Versus Alone: A Double-blind, Randomized, Pharmacokinetic, and Tolerability Comparison
Chao Chen et al.
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