ABSTRACT
The aim of the present work was to prepare a nasal spray of bisoprolol fumarate (BF). The Pharmacokinetics and relative bioavailability of the BF nasal formulation were evaluated in Wistar rats. The BF nasal spray after administration exhibited very fast absorption and higher plasma drug concentration. The maximum plasma concentration (C(max)) and the time to reach it (T(max)) were 409.5 ng/ml and 3.6 min for the BF nasal spray, 39.4 ng/ml and 26.7 min for the drug solution, respectively. The bioavailability of the BF nasal spray was greater than 1500.0%. Meantime, the effect of the BF nasal spray on nasal mucociliary movement was also studied with a toad palate model. The BF nasal preparation showed minor ciliotoxicity, but the adverse effect was temporary and reversible.
Subject(s)
Adrenergic beta-1 Receptor Antagonists/administration & dosage , Bisoprolol/administration & dosage , Administration, Intranasal , Adrenergic beta-1 Receptor Antagonists/blood , Adrenergic beta-1 Receptor Antagonists/chemistry , Adrenergic beta-1 Receptor Antagonists/pharmacokinetics , Adrenergic beta-1 Receptor Antagonists/toxicity , Aerosols , Animals , Biological Availability , Bisoprolol/blood , Bisoprolol/chemistry , Bisoprolol/pharmacokinetics , Bisoprolol/toxicity , Bufonidae , Chemistry, Pharmaceutical , Mucociliary Clearance/drug effects , Nasal Mucosa/drug effects , Nasal Mucosa/metabolism , Rats, Wistar , Risk Assessment , Technology, Pharmaceutical/methods , Toxicity TestsABSTRACT
The pharmacodynamics of prostaglandin E1 (PGE1) administered by different routes to rats was investigated in this paper. The hypotensive effect of PGE1 was used as an index of drug efficacy, pharmacodynamic parameters such as time to reach peak effect (Tmax), maximal percentage of blood pressure decrease (Emax, %), duration of effect (Td), and the area determined after PGE1 given to rats intranasally, sublingually, intraperitoneally (ip),and intramuscularly (im), separately, and compared with those obtained from intravenous (iv) administration. Similar to iv route, the pharmacodynamic parameters of PGE1 from the other administration routes, Emax, Td and in particular AUC values were all increased with increasing doses, showing dose-efficacy relationship. Tmax was found to be approximately 3-4 min for nasal route, 3-8 min for im, 6-8 min for ip and 12-30 min for sublingual route, separately. Thus, the order of magnitude of absorption rate of the drug was as follows: nasal≈im＞ip＞sublingual. If the pharmacological bioavailability (PF) for each administration route was used as a tentative measure of drug absorption extent, the order of magnitude of absolute bioavailability appeared as follows: nasal＞im≈ip＞sublingual. Furthermore, the interindividual difference was found to be larger for im and ip route than that for nasal and sublingual route. These results indicate nasal and sublingual routes are two promising routes for the systemic delivery of PGE1 in clinical applications.
ABSTRACT
The effect of CeCl3 on the rooting and nitrogen metabolism of the peach plantlet in vitro was studied when the CeCl3 was added to the rooted medium. The results showed that the rooting rate and the fresh weight of roots could be increased and the length of root could be enlarged, and the activities of nitrate reductase, glutamine synthetase, glutamate dehydrogenase in the roots were increased significantly, the transformation of NO(3-) to NH(4+) and protein were promoted, and the nitrogen metabolism was accelerated when the plantlets grew in the optimum rooted medium that contained the concentration 0.3 micromol/L Ce(3+).
Subject(s)
Cerium/pharmacology , Nitrogen/metabolism , Prunus/metabolism , Glutamate Dehydrogenase/metabolism , Glutamate-Ammonia Ligase/metabolism , Nitrate Reductase , Nitrate Reductases/metabolism , Nitrates/metabolism , Plant Proteins/metabolism , Plant Roots/drug effects , Plant Roots/enzymology , Plant Roots/growth & development , Prunus/enzymology , Prunus/growth & development , Quaternary Ammonium Compounds/metabolismABSTRACT
OBJECTIVE: To prepare the inclusion compound of diclofenac sodium (DFS)-β-cyclodextrin (β-CD) and investigate its properties. METHOD: The inclusion compound of DFS-β-CD was prepared by the co-precipitation method. RESULTS: The inclusion compound of DFS-β-CD was confirmed by UV absorption spectrum, IR absorption spectroscopy, differential scanning calorimetry (DSC) and phase solubility diagram. Meanwhile, the content analysis of the inclusion compound showed that the molecular ratio of DFS to β-CD was 1∶1. CONCLUSION: The soluability and dissolution rate of DFS were increased and its irritation to stomach was reduced when the drug was included by β-CD.
