Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Traditional IUPAC Name
Độ hòa tan
pKa (strongest acidic)
pKa (Strongest Basic)
Dược Lực Học :
Pregabalin is a new anticonvulsant drug indicated as an add on therapy for partial onset seizures and for certain types of neuropathic pain. It was designed as a more potent successor to a related drug, gabapentin. Pregabalin binds to the alpha2-delta subunit of the voltage-gated calcium channel in the central nervous system. While pregabalin is a structural derivative of the inhibitory neurotransmitter gamma- aminobutyric acid (GABA), it does not bind directly to GABAA, GABAB, or benzodiazepine receptors, does not augment GABAA responses in cultured neurons, does not alter rat brain GABA concentration or have acute effects on GABA uptake or degradation. However, in cultured neurons prolonged application of pregabalin increases the density of GABA transporter protein and increases the rate of functional GABA transport. Pregabalin does not block sodium channels, is not active at opiate receptors, and does not alter cyclooxygenase enzyme activity. It is inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Cơ Chế Tác Dụng :
Pregabalin is an anticonvulsant drug used for neuropathic pain, as an adjunct therapy for partial seizures, and in generalized anxiety disorder. It was designed as a more potent successor to gabapentin. Pregabalin is marketed by Pfizer under the trade name Lyrica. It is considered to have a dependence liability if misused, and is classified as a Schedule V drug in the U.S. [Wikipedia]
Pregabalin binds with high affinity to the alpha2-delta site (an auxiliary subunit of voltage-gated calcium channels) in central nervous system tissues. Although the mechanism of action of pregabalin is unknown, results with genetically modified mice and with compounds structurally related to pregabalin (such as gabapentin) suggest that binding to the alpha2-delta subunit may be involved in pregabalin's antinociceptive and antiseizure effects in animal models. In vitro, pregabalin reduces the calcium-dependent release of several neurotransmitters, possibly by modulation of calcium channel function. Studies also suggest that the descending noradrenergic and serotonergic pathways originating from the brainstem may be involved with the mechanism of pregabalin. Interestingly, although pregabalin is a structural derivative of inhibitory neurotransmitter gamma-aminobutyric acid (GABA), it does not bind directly to GABA or benzodiazepine receptors. The sodium channels, opiate receptors, and cyclooxygenase enzymes are not involved with the mechanism of pregabalin. It is also inactive at serotonin and dopamine receptors and does not inhibit dopamine, serotonin, or noradrenaline reuptake.
Dược Động Học :
▧ Absorption :
Pregabalin is well absorbed after oral administration. When an oral administration of pregabalin under fasting conditions is given, the pharmacokinetic parameters are as follows:
Tmax = 1.5 hours;
Oral bioavailability = >90% (independent of dose);
Time to steady state = 24-48 hours.
It is also a substrate for the L-type transport system.
▧ Volume of Distribution :
Apparent volume of distribution, oral administration = 0.5 L/kg.
Pregabalin has been shown to cross the placenta in rats and is present in the milk of lactating rats.
▧ Protein binding :
Pregabalin does not bind to plasma proteins.
▧ Metabolism :
Pregabalin undergoes negligible metabolism in humans.
▧ Route of Elimination :
90% of the dose was recovered in the urine as the parent compound. The N-methylated derivative of pregabalin, the major metabolite was found in the urine and accounted for 0.9% of the dose. Pregabalin (S-enantiomer) did not undergo racemization to the R-enantiomer.
▧ Half Life :
▧ Clearance :
Renal clearance, healthy subjects = 67.0 - 80.9 mL/min. Because pregabalin is not bound to plasma protein, this rate suggests the involvement of renal tubular reabsorption.
Độc Tính :
Most common adverse reactions (≥5% and twice placebo) are dizziness, somnolence, dry mouth, edema, blurred vision, weight gain and thinking abnormal (primarily difficulty with concentration/attention).
Chỉ Định :
Pregabalin is used for the management of neuropathic pain associated with diabetic peripheral neuropathy or spinal cord injury, and postherpetic neuralgia. It is also used as adjunctive therapy for adult patients with partial onset seizures and management of fibromyalgia.
Tương Tác Thuốc :
The CNS depressants, Triprolidine and Pregabalin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Liều Lượng & Cách Dùng :
Capsule - Oral - 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg
Solution - Oral - 20 mg/mL
Tài Liệu Tham Khảo Thêm
National Drug Code Directory