INDICATIONS: TREMEPEN is indicated for the treatment of neuropathic pain, diabetic neuropathy, postherpetic neuropathy, trigeminal neuralgia, HIV neuralgia, phantom limb pain and neuropathic back pain.
Bioavailability of gabapentin is not proportional to dose: As the dose increases, bioavailability decreases. With doses of 900 mg / day divided in 3 administrations, bioavailability reaches 60% decreasing to 27% at doses of 4,800 mg / day. Gabapentin administration with food slightly increases its absorption. Gabapentin binds very little to plasma proteins (3%) being its apparent volume of distribution after intravenous dose of 150 mg of 58 ± 6. Gabapentin is not appreciably metabolized and eliminated by renal excretion.
The elimination half-life is 5-7 hours and is unaffected when multiple doses. Both plasma clearance and renal are proportional to creatinine clearance. The elimination of gabapentin is lower in patients with renal dysfunction and in the elderly.
Gabapentin is eliminated in hemodialysis, so in these patients and in patients with renal impairment may need adjustments doses.
After oral administration of tramadol, the drug is rapidly absorbed with an initial 68% bioavailability of reaching 100% after several doses. This increased bioavailability is due to hepatic metabolization tramadol experiences a saturable first-pass. The bioavailability increases with age and decreases in patients with renal or hepatic impairment. After intramuscular administration, the bioavailability is 100%. The presence of food in the stomach does not affect the absorption of tramadol. Maximum concentrations of the active metabolite of tramadol (M1) obtained at 3 hours after an oral dose, while the native drug is detectable at 15-45 minutes and reaches its maximum after 2 hours. The maximum analgesic effect coincides with the peak plasma concentrations of M1, and is maintained for about 6 hours. The concentrations of equilibrium (steady state) are reached within 2 days of starting treatment with multiple doses. Binding to plasma proteins is small (20%). The drug crosses the placental barrier and is excreted in breast milk at 0.1%
Tramadol undergoes hepatic metabolism significant first step. First, the O-desmethyl and N-desmethyl metabolites are formed. This metabolism is stereoselective experiencing the (-) A selective O-demethylation, while the (+) enantiomer preferentially undergoes N-demethylation. In a second stage, the O-demethylated metabolites are conjugated for disposal. Of the 11 identified metabolites of tramadol only metabolite M1 (O-demethyltramadol) has analgesic activity that is apparently critical for tramadol analgesia. Demethylation of tramadol to cause M1 depends on the enzyme cytochrome P450 CYP2D6 and, therefore, those drugs which inhibit this system, reduce the analgesic efficacy and increase the specific side reactions of native tramadol (i.e. unmetabolized) . In normal adults, the half-life of tramadol and its metabolite M1 ranging between 5 and 7 hours. Both the native drug and its metabolites are primarily excreted in the urine (90%) appearing in the stool only 10% of the administered dose.