METHODS: Solid dispersions were prepared using hydrophilic carriers like polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974pNF (CP) in various ratios using solvent evaporation technique. These formulations were evaluated using solubility studies, dissolution studies; Fourier transmitted infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetery (DSC). The influence of polymer type and drug to polymer ratio on the solubility and dissolution rate of norfloxacin was also evaluated.
RESULTS: FTIR analysis showed no interaction of all three polymers with norfloxacin. The results from XRD and DSC analyses of the solid dispersion preparations showed that norfloxacin existsin its amorphous form. Among the Norfloxacin: PEG solid dispersions, Norfloxacin: PEG 1:14 ratio showed the highest dissolution rate at pH 6.8. For norfloxacin: PVP solid dispersions, norfloxacin: PVP 1:10 ratio showed the highest dissolution rate at pH 6.8. For Norfloxacin: CP solid dispersions, norfloxacin: P 1:2 ratio showed the highest dissolution rate at pH 6.8.
CONCLUSION: The solid dispersion of norfloxacin with polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974p NF (CP), lends an ample credence for better therapeutic efficacy.
METHODS: Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro.
RESULTS: The area under the plasma nifedipine concentration-time curve (AUC0-alpha) in nafcillin-pretreated subjects (80.9 +/- 32.9 micro g l-1 h-1) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 micro g l-1 h-1) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h-1 vs 56.5 +/- 32.0 l h-1) (P < 0.002).
CONCLUSIONS: The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.
PRINCIPAL FINDINGS: The serum antigen concentration-time profile of the N. sumatrana venom and its major toxins injected intravenously fitted a two-compartment model of pharmacokinetics. The systemic clearance (91.3 ml/h), terminal phase half-life (13.6 h) and systemic bioavailability (41.9%) of N. sumatrana venom injected intramuscularly were similar to those of N. sputatrix venom determined in an earlier study. The venom neurotoxin and cardiotoxin reached their peak concentrations within 30 min following intramuscular injection, relatively faster than the phospholipase A2 and whole venom (Tmax=2 h and 1 h, respectively). Rapid absorption of the neurotoxin and cardiotoxin from the injection site into systemic circulation indicates fast onsets of action of these principal toxins that are responsible for the early systemic manifestation of envenoming. The more prominent role of the neurotoxin in N. sumatrana systemic envenoming is further supported by its significantly higher intramuscular bioavailability (Fi.m.=81.5%) compared to that of the phospholipase A2 (Fi.m.=68.6%) or cardiotoxin (Fi.m.=45.6%). The incomplete absorption of the phospholipase A2 and cardiotoxin may infer the toxins' affinities for tissues at the injection site and their pathological roles in local tissue damages through synergistic interactions.
CONCLUSION/SIGNIFICANCE: Our results suggest that the venom neurotoxin is absorbed very rapidly and has the highest bioavailability following intramuscular injection, supporting its role as the principal toxin in systemic envenoming.
MATERIALS AND METHODS: A randomized, 2-treatment, 2-period, 2-sequence, single dose, crossover with a washout period of 2 weeks, was conducted in 24 healthy Thai male volunteers. Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72 and 96 h following drug administration. Plasma concentrations of risperidone and 9-hydroxyrisperidone were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of risperidone and 9-hydroxyrisperidone were determined using a non-compartmental model.
RESULTS: The geometric means ratios (%) and 90% confidence interval (CI) of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of risperidone were 104.49 % (92.79% - 117.66%), 100.96 % (92.15% - 110.61 %) and 97.99 % (90.72% - 105.85%). The 90% CI of geometric means ratios of the test and reference products for the log-transformed pharmacokinetic parameters, Cmax, AUC0-t and AUC0-inf of 9-hydroxyrisperidone were 97.00%, 96.97% and 97.49%.
CONCLUSIONS: The 90% CI for the geometric means ratios (test/reference) of the log-trasformed Cmax, AUC0-t and AUC0-inf of risperidone and its major active metabolite were within the bioequivalence acceptance criteria of 80% - 125% of the US-FDA.