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In our preliminary studies, we observed zolmitriptan (ZOL) treatment led to induction of CYP3A2 in male not female rats. To figure out the reason is of great significance for drug-drug interactions and personalized administration. Since growth hormone (GH) is known as the major mechanistic determinant of sexually-dimorphic gene expression like CYP3A2 in rat liver, the impacts of ZOL on both plasma GH levels in non monosodium glutamate (MSG)-treated rats and CYP3A2 expression in GH depleted MSG-treated rats were studied. ZOL was shown to partially suppress GH levels in both genders. Furthermore, CYP3A2 protein and mRNA level declined in male not female MSG-treated rats. In order to study the possible molecular events involved in the depression of GH and gender-selective induction on rat CYP3A2 by ZOL, the mRNA and protein level (whole protein and nuclear protein) of hepatocyte nuclear factor 4α (HNF4α) was investigated. Nuclear accumulation of HNF4α was observed in the normal male not female rat liver tissue following ZOL treatment. However, this kind of nuclear translocation did not occur in rat hepatocytes and MSG-treated rats. These findings demonstrated CYP3A2 inducibility by ZOL was gender-selective. GH and HNF4α may play an important role in CYP3A2 induction.
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OBJECTIVE:To prepare zolmitriptan-diclofenac microemulsion,and conduct quality evaluation and in vitro trans-dermal study. METHODS:Using solubility and microemulsion area in pseudo-ternary phase diagram as indexes,the types of oil phase and mixed emulsifier ratio of zolmitriptan-diclofenac microemulsion were screened;the microemulsion quality was inspected using particle size,Zeta potential,appearance and stability. HPLC was used to measure the contents of zolmitriptan and diclofenac. Transdermal diffusion test instrument was used,2 g microemulsion was smeared in cuticle of extracouporeal rats'skin,and cumula-tive transdermal rate in 24 h was determined. RESULTS:The microemulsion formulation was as follow as 10% oil phase(octanoic acid triglyceride),25% mixture emulgator [polysorbate 80-brij 97 (1:1)],8.3% propylene glycol and 25 mg zolmitriptan,1.25 mg diclofenac,and water adding to 100 mL. The average particle size of prepared microemulsion was(28.2±2.5)nm,Zeta poten-tial was(-3.25±0.33)mV,the appearance was rounding;the microemulsion showed no stratification or flocculation at room tem-perature after placed for 1 month. Contents of zolmitriptan and diclofenac were 0.248 mg/mL,12.46 mg/mL(n=3);24 h cumula-tive transdermal rates were 80%,75%. CONCLUSIONS:Zolmitriptan-diclofenac microemulsion is prepared,and its in vitro trans-dermal ability is good.
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Cluster headache causes severe unilateral temporal or periorbital pain, lasting 15 to 180 minutes and accompanied by autonomic symptoms in the nose, eyes, and face. Headaches often recur at the same time each day during the cluster period, which can last for weeks to months. Some patients have chronic cluster headache without remission periods. The pathophysiology of cluster headache is not fully understood, but may include a genetic component. Cluster headache is more prevalent in men and typically begins between 20 and 40 years of age. Treatment focuses on avoiding triggers and includes abortive therapies, prophylaxis during the cluster period, and long-term treatment in patients with chronic cluster headache. Evidence supports the use of supplemental oxygen, sumatriptan, and zolmitriptan for acute treatment of episodic cluster headache. Verapamil is first-line prophylactic therapy and can also be used to treat chronic cluster headache. More invasive treatments, including nerve stimulation and surgery, may be helpful in refractory cases.
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OBJECTIVE: To prepare microspheres for nasal delivery by emulsification solvent evaporation technique using water-soluble carboxylation chitosan as the drug carrier, thus to avoid using stimulatory and toxic aldehydes crosslinkers and acid solvent which are used by the traditional method. METHODS: Zolmitriptan (ZT) was used as the model drug to prepare the carboxylation chitosan microspheres. The prescription and technology were optimized to prepare the microspheres. The yield, particle sizes, appearance, drug loading, encapsulation efficiency and drug release of the microspheres were evaluated. RESULTS: The microspheres prepared by the optimized method were spherical, smooth, and free flowing. The particle sizes of the microspheres were well-distributed and the mean particle size was (21.4±10.1)μm. The drug loading was 5.67% and the encapsulation efficiency was 62.4%. The in vitro release study of the microspheres showed that the drug was sustainedly released and could be released for about 85% in 8 h. CONCLUSION: It is feasible to prepare carboxylation chitosan microspheres for nasal administration by emulsification solvent evaporation method, avoiding the use of aldehydes crosslinkers and acid solvent.
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Objective:To determine the equilibrium solubility of zolmitriptan in various media and its partition coefficients for the n-octanol-water/buffer solution systems.Methods:A high performance liquid chromatography was established and used to detect the concentration of zolmitriptan;the partition coefficients for the n-octanol-water/buffer solution systems of zolmitriptan were determined by shaking flask method.Results:The equilibrium solubility of zolmitriptan in water was 12.6 g/L at 37℃.The equilibrium solubility of zolmitriptan were 1 382.0,553.0,85.2,71.5,47.1,11.5 and 4.85 g/L in buffer solutions with pH values of 3.6,4.5,6.0,6.8,7.4,8.0 and 9.0 respectively.Papp of zolmitriptan was 0.013 in water and were 0.04,0.06,0.14,0.20,0.23,0.25 and 1.44 in buffer solutions with different pH values.Conclusion:In the range of pH3.6 to pH 9.0,the equilibrium solubility of zolmitriptan was decreased while the apparent oil/water partition coefficient was increased with the increasing of pH values.
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Aim:To develop a practical chiral CE method for the quantitative determination of the unwanted enantiomer[( R )-enantiomer]presented in zolmitriptan. Methods:The background electrolyte was 20 mmol/L sodium dihydrogenphosphate solution with 1% S-β-CD,adjusted to pH 3.50 with phosphoric acid. A fused-silica capillary(60 cm×50 μm ID,effective length 51.5 cm)was used at 20 ℃ for the separation. The applied voltage was -30 kV. The samples were loaded by hydrodynamic injection(50 mbar pressure,6 s). UV was measured at 220 nm. Results:Zolmitriptan and its chiral impurity were baseline resolved ( R s=6.66). The linearity was good over the concentration range from 4 to 80 μg/mL( r =0.999 8) of ( R )-enantiomer. The injection precision (expressed as CV%) was 2.83%. The average recovery was 99.97%( n =9). The limit of detection was 1.5 μg/mL. The host-guest complex binding constants were 964 and 905 mol-1 for ( R )-enantiomer and zolmitriptan,respectively. Conclusion:The method is suitable for the determination of ( R )-enantiomer in zolmitriptan and binding constants of zolmitriptan enantiomers to S-β-CD.
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OBJECTIVE:To study the bioavailability of the domestic and the imported zolmitriptan tablets in human body.METHODS:The plasma concentration of zolmitriptan in24healthy male volunteers were determined by HPLC-FI after o?rally administered with single dose of5mg zolmitriptan tablets by randomized crossover way,the pharmacokinetics parameters and the relative bioavailability of which were calculated.RESULTS:The plasma concentration-time curves of the oral zolmitriptan tablets fitted one-compartment open model of linear dynamics,the main parameters of domestic tablets and im?ported tablets were described as follows,C max (8.273?3.379)ng/ml and(7.756?2.623)ng/ml,t max (2.341?1.169)h and(2.644?1.121)h,AUC 0～t (47.95?15.75)(ng?h)/ml and(46.27?13.71)(ng?h)/ml,the relative bioavailability of do?mestic zolmitriptan tablets and the imported tablets was(106.72?32.03)%.CONCLUSION:The domestic and the imported zomitriptan tablets is bioequivalent.
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BACKGROUND: Zolmitriptan (Zomig) is a selective serotonin agonist at the 5-hydroxytryptamine (5-HT1B/1D) receptor that acts both centrally and peripherally in the trigeminal nucleus and axon terminals and at adjacent meningeal vessels. The clinical efficacy of zolmitriptan in adult migraine has been documented in several placebo-controlled studies, but not studied yet in Korea. METHODS: This multicenter, double-blind, placebo-controlled study was directed to evaluate the efficacy and tolerability of a single 2.5-mg dose of zolmitriptan for the acute treatment of a single moderate or severe migraine attack in Korean patients. A sample consisting of 129 outpatients was randomized to receive either zolmitriptan (n=67) or placebo (n=62). RESULTS: The headache response at 2 hours after treatment was significantly greater in patients receiving zolmitriptan than in patients receiving placebo (52.2% versus 30.7%, p<0.05). At 4 hours, the response rate in the zolmitriptan group (91.5%) was significantly higher than in the placebo group (65.6%; p<0.05). Among the nonheadache symptoms, phonophobia was more relieved in the zolmitriptan group than in the placebo group (p=0.038). There were no clinically serious adverse events that were judged by the physicians to be related to zolmitriptan. CONCLUSIONS: The results of this study demonstrate that zolmitriptan tablets 2.5-mg taken for acute migraine attacks are effective and well-tolerated in Korean patients. (J Korean Neurol Assoc 19(1):29~35, 2001
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Adult , Humans , Headache , Hyperacusis , Korea , Migraine Disorders , Outpatients , Presynaptic Terminals , Serotonin , Serotonin Receptor Agonists , Tablets , Trigeminal NucleiABSTRACT
0.05). The relative bioavailability of Zolmitriptan dispersible tablet was (95.54?10.99)%. CONCLUSION: Zolmitriptan dispersible tablet and Zolmitriptan general tablet were bioequivalent.