• Journal of Pharmaceutical Investigation
• /
• v.27 no.4
• /
• pp.295-301
• /
• 1997

Nitrendipine, a slightly soluble calcium channel blocking agent forms a solid dispersion system with $hydroxypropyl-{\beta}-cyclodextrin$, which exhibits better dissolution characteristics than the uncomplexed drug. The dissolution rate of nitrendipine was markedly increased in solid dispersion system in pharmacopeial disintegration media at pH 1.2 and pH 6.8. Four different dosage forms of nitrendipine were administered to rats: (a) nitrendipine in the solution of PEG 400; (b) nitrendipine solid dispersion system with $hydroxypropyl-{\beta}-cyclodextrin$ in a molar ratio of 1:2 by solvent evaporation method and administered in capsule form; (c) physical mixture of nitrendipine with $hydroxypropyl-{\beta}-cyclodextrin$ in a molar ratio of 1:2 and administered in capsule form; (d) nitrendipine alone administered in capsule form. Relative bioavailability after the oral administration of various dosage forms to rats with a dose of 10 mg/kg equivalent to nitrendipine was compared with that of nitrendipine in the solution of PEG 400. The AUC of solid dispersion was significantly bigger than that of nitrendipine powder. $T_{max}$ of solid dispersion was significantly shorter and $C_{max}$ was higher than that of nitrendipine powder. These results indicate that the bioavailability of nitrendipine could be improved markedly by inclusion complexation. An interesting correlation also appears to exist between the in vitro dissolution data and the area under the plasma concentration-time curves.

• Journal of Pharmaceutical Investigation
• /
• v.31 no.3
• /
• pp.167-172
• /
• 2001

All-trans retinoic acid (ATRA), vitamin A acid, has been shown to exert anticancer activity in a number of types of cancers, particularly in acute promyelocytic leukaemia (APL). Due to its highly variable bioavailability and induction of its own metabolism after oral treatment, development of parenteral dosage forms are required. However, its poor aqueous solubility and chemical unstability give major drawbacks in parenteral administration. This study was undertaken to investigate a possibility to develop a parenteral formulation of ATRA by employing solid lipid nanoparticle (SLN) as a carrier. By optimizing the production parameters and the composition of SLNs, SLNs with desired mean particle size (<100 nm) as a parenteral dosage form could be produced from trimyristin (as solid lipid), Egg phosphatidylcholine and Tween 80 (as SLN stabilizer). The mean particle size of SLN formulation of ATRA was not changed during storage, suggesting its physical stability. Thermal analysis confirmed that the inner lipid core of SLNs exist at solid state. The mean particle size of ATRA-loaded SLNs was not significantly changed by the lyophilization process. ATRA could be efficiently loaded in SLNs, while maintaining its anticancer activity against HL-60, a well-known APL cell line. Furthermore, by lyophilization, ATRA loaded in SLN could be retained chemically stable during storage. Taken together, our present study demonstrates that physically and chemically stable ATRA formulation adequate for parenteral administration could be obtained by employing SLN technology.

• The Korean Journal of Pain
• /
• v.8 no.1
• /
• pp.43-50
• /
• 1995

The purpose of this study was to compare postoperative analgesic effect according to intravenous doses of ketorolac. The ninety-eight adult patients, scheduled for elective surgery under general anesthesia, were randomly assigned to receive saline or one of the five doses of ketorolac (10, 15, 30, 45, 60mg). After recoverg from anesthesia, saline or ketorolac was injected intravenously, and the visual analogue score, sedation secore, mean blood pressure, heart rate, and the incidence of nausea and vomiting were measured 30 minutes, 1 hour and 2 hours the injection. Saline or 10 mg of ketorolac had no postanalgesic effect. Above 15 mg of ketorolac had analgesic effect, but this analgesic effect was not increased with increasing doses of ketorolac (30, 45, 60 mg). Any side effects (nausea, vomiting, excessive sedation, cardiopulmonary depression, and renal and hematologic adverse events) was not observed associated with ketorolac administration. These results suggested that 15 mg of ketorolac is the most reliable dose for postoperative anlgesia in intravenous administration.

• Journal of Environmental Health Sciences
• /
• v.21 no.3
• /
• pp.28-37
• /
• 1995

This study is performed to find out the effects of selenium against cadmium toxicity. The experimental mice were divided into 6 gruops such as control group, cadmium alone treatment group, selenium treatment groups and two simultaneous treatment groups of selenium and cadmium. Mice were given intraperitoneal administration with two dosage of sodium selenite such as 1.0 mg/kg, 2.5 mg/kg body weight and cadmium chloride was administered 3.0 mg/kg body weight. After giving the challenge dose, the concentration of cadmium and metallothionein and histopathological change of liver and kidney were determined. The results were summarized as follows on 1. The simultaneously administration of selenium and cadmium significantly more decreased cadmium concentration in kidney and iiver tissues compared to the administration of cadmium only(P<0.05). 2. The simultaneously administration of selenium and cadmium more increased metallothionein concentration compared to administration of cadmium only. 3. The simultaneously administration of selenium and cadmium more decreased cadmium concentration in urine compared to the administration of cadmium only. 4. When liver and kidney tissues were observed with optical microscope, no obvious changes were visible in those tissues.

• Journal of Pharmaceutical Investigation
• /
• v.24 no.4
• /
• pp.289-295
• /
• 1994

Pharmacokinetic drug interaction between phenytoin and verapamil was investigated following i.v. administration of two drugs concomitantly to rabbits. Verapamil was coadministered with phenytoin (5 mg/kg) to rabbits at the doses of 0.5,1 and 2 mg/kg, respectively. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 1mg and 2mg/kg of verapamil, respectively. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin should be administered with verapamil in clinical practice.

• Journal of Pharmaceutical Investigation
• /
• v.23 no.1
• /
• pp.27-32
• /
• 1993

Pharmacokinetic drug interaction between phenytoin and diltiazem was investigated following i.v. administration concomitantly to rabbits. Diltiazem was coadministered at doses of 1, 2 and 3 mg/kg, respectively, with phenytoin (5 mg/kg) to rabbits. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 2 mg and 3 mg/kg of diltiazem. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be practiced for reduction of side or toxic effect when phenytoin should be administered with diltiazem in clinical practice.

• YAKHAK HOEJI
• /
• v.36 no.4
• /
• pp.321-325
• /
• 1992

Pharmacokinetic interaction of theophylline with pefloxacin following i.v. administrations was investigated in rabbits. Pefloxacin was coadministrated at doses of 10 and 20 mg/kg or previously administered for 6 days 10 and 20 mg/kg. Plasma concentration and AUC of theophylline were increased significantly (p<0.05) and the renal clearance $(CL_r)$, total body clearance $(CL_r)$ and the volume of distribution $(Vd_{ss})$ were decreased significantly (p<0.005) by the pretreatment. It demonstrates that adjustment of dosage regimen of theophylline should be considered when concomitant administration of pefloxacin is prescribed.

• Korean Journal of Clinical Pharmacy
• /
• v.13 no.2
• /
• pp.67-71
• /
• 2003

The purpose of this study was to investigate the effect of aspirin (5, 10, 20 mg/kg) on the pharmacokinetics of metformin $(15\;mg/kg)$ in rabbits. The plasma concentration of metformin was decreased significantly (p<0.05) by co-administration of aspirin (10, 20 mg/kg) compared with control. Area under the plasma concentration-time curve (AUC) of metformin was decreased significantly (p<0.05) by co-administration of aspirin (10, 20mg/kg) compared with control. Relative bioavailability $(R.B\%)$ of metformin by co-administration was 79.3 (5 mg/kg), 57.5 (10 mg/kg) and 62.5 (20 mg/kg). Peak plasma concentration of metformin was significantly (p<0.05) decreased by co-administration of aspirin (10, 20 mg/kg) compared with control. The elimination rate constant $(K_{el})$ of metformin was increased by co-administration of aspirin (10, 20 mg/kg) compared with control. The terminal half-lifes $(t_{1/2})$ and mean resident time (MRT) of metformin by co-administration of aspirin (10, 20 mg/kg) were decreased significantly (p<0.05) compared with control. It is considered that the significantly decreased plasma concentration and AUC of metrormin is due to increase of elimination in urine acidified by co-administration of aspirin. The results suggest that the dosage of metformin should be adjusted when metformin is co-administered with aspirin in the clinical situation.

• Korean Journal of Clinical Pharmacy
• /
• v.11 no.2
• /
• pp.57-61
• /
• 2001

The effect of circadian rhythm on the pharmacokinetics of acebutolol was studied in rabbits administered intravenous 5 mg/kg dose of acebutolol at 09:00 in the morning (a.m) and 22:00 in the evening (p.m). A significant effect of circadian rhythm of pbarmacokinetic parameters as a function of time of day was noted in rabbits, showing lower total body clearance (CLt), higher plasma concentration and the area under the plasma concentration time curve (AUC) when acebutolol was given in the evening. The plasma concentration of acebutolol was increased significantly (p<0.05) at 12-24 hr after dosing in the evening. The AUC was greater in the evening $(111\%)$ than that in the morning and $CL_t$, was higher when acebutolol was given in the morning ($1.12\pm0.24$ ml/hr) versus in the evening ($1.01\pm0.22$ ml/hr), but those were not significant. Therefore, It is reasonable to consider individual circadian rhythm for effective dosage regimen of acebutolol in clinical chronotherapeutics.

• The Journal of the Korean dental association
• /
• v.19 no.2 s.141
• /
• pp.163-166
• /
• 1981

Sugar consumption has been increased in recent days according to an improvement in living conditions. It is generally accepted that sugar is one of the causes of caries and that diabetes mellitus is closely related to the periodontal diseases. This investigation was designed to gain informations on the influence of overdosage of sugar and/or high blood sugar level on the periodontal tissue. 12 rats weighing about 1.5Kg were divided into 4 groups, control one and 3-day, 7-day, 14-day ones after daily administration of 30-50 gm of sucrose. The results were as follows: 1. Daily adminisration of 30-50 gm of sucrose elevated blood glucose level as much as 10-20 mg% than before. 2. Epithelial keratinization was gradually conspicuous to the dosage of sucrose. 3. The severity of inflammatory infiltration was also increased to the dosage of sucrose. 4. Inflammatory infiltration was encountered in marginal gingiva more than other periodontal tissue.