• Journal of Pharmaceutical Investigation
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• 제21권2호
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• pp.73-78
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• 1991

The influence of different suppository bases on the rectal absorption and the dissolution rate of propranolol was investigated. The bioavailability of propranolol in rectal suppository was determined by comparing the area under the concentration-time curves(AUC) for oral administration with rectal suppositories in rabbits. The dissolution $rates(D_{20min})$ were higher in such order as tween (TWE), witepsol H-15(WIT), polyethylene glycol(PEG) suppository. The maximum blood concentrations $(C_{max})$ were 803.9 ng/ml for TWE suppository, 770.2 ng/ml for WIT suppository, 281.2 ng/ml for PEG suppository and 177.1 ng/ml for oral administration. The relative bioavailabilities were 233.5% for TWE suppository, 218.1% for TWE suppository, 191.3% for PEG suppository. The correlation between $D_{20min}$ and AUC, the time for dissolution in 75% and $C_{max}$, the mean dissolution time and the mean residence time showed significant linear relationship respectively.

• Journal of Pharmaceutical Investigation
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• 제16권4호
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• pp.148-151
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• 1986

This paper was designed to investigate the influence of different suppository bases on both the rectal absorption and dissolution rate of lithium carbonate, and to compare bioavailability from rectal administration with that from oral administration. The dissolution rates were in such order as PEG 4000, surfactant A (Witepsol 15+sodium lauryl sulfate), surfactant B (Witepsol 15+cholic acid), Witepsol 15 and cacao butter. Among various suppository bases, the blood level of lithium carbonate after rectal administration was increased in the following order: surfactant A>surfactant B>PEG 4000>Witepsol 15>cacao butter. When it comes to compare oral with rectal administration in AUC values, surfactants and PEG 4000 showed similar blood levels to oral administration, but lipophilic bases such as Witepsol 15 and cacao butter showed far lower blood level than oral administration. Peak time in oral administration was 2 hrs, but those in rectal administration using various suppository bases were $6{\sim}8$ hrs.

• Archives of Pharmacal Research
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• 제18권4호
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• pp.219-223
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• 1995

Rectal absorption of opeprazole, a proton pump inhibitor, from suppositories was studied in rabbits. The suppositories were prepared by the conventional melting method with two types of bases, water-soluble polyethylene glycol (PEG) 4000 and oil-soluble Witepsol H15 bases, and administered intractally (ir) to rabbits at a dose of 10 mg omeprazole/kg. The plasma omeprazole concentration-time profiles of the two suppositories were compared with those following intravenous 9iv) administration of the same dose. There were no significant differences between the two suppositories in bioabailabilities and peak plasma concentrations $(C_{max})$. Bioavaiabilities and $C_{max}$ of PEG- and Witpsol suppositories were 30.3 and 33.9%, and 7.0 and $5.6\mug/ml$, resepectively. However, PEG suppository showed significantly (p<0.05) shorter time to reach peak plasma concentration $(T_{max})$ mean absorption time (MAT) and mean residence time in the plasma (MRT) than Witepsol suppository. The $T_{max}$ MRT nad MAT were 25.0, 83.0 and 38.5 min for PEG syppository, but were 90.0, 122.5 and 78.0 min for Wiepsol supposiotory, respectively. These differences between thw two suppositories could be explanined by the difference in the in vitro dissolution rates between the suppositories. The dissolution of omeprazole form PEG suppository was reportedly much faster than that from Witepsol suppository. It suggests that plasma profiles of omeprazole, especially $C_{max}$ MAT and MRT, could be controlled by modifying the in vitro dissolution rate of the drug from the suppositories. Above results suggest that rectal suppository is worth developing as an alternative dosage form of omeprazole to the conventional oral preparations which need sophisticated treatments, such as enterix coating, to prevent acid degradation of the drug in the stomach fluid.

• Journal of Pharmaceutical Investigation
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• 제18권2호
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• pp.61-67
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• 1988

The influence of different suppository bases on the dissolution, and the bioavailability of aspirin suppositories in rabbits and humans was investigated using Witepsol H15 (WIT), WIT-Tween 80 (TWE), WIT-sodium lauryl sulfate (SLS), polyethylene glycol (PEG), hollow WIT (WIT-HOLL) and capsule incorporated into WIT (WIT-CAP). The results obtained were as follows: 1) Dissolution rates of aspirin suppositories with different bases in distilled water were faster in the order of WIT-TWE >WIT-SLS >PEG >WIT-HOLL >WIT >WIT-CAP. 2) The maximum blood levels $(C_{max})$ of aspirin in rabbits and humans were highest in WIT-TWE and WIT-SLS bases, but $C_{max}$ from WIT base was lower than that in oral administration of aspirin suspension. 3) The times reaching the maximum blood levels $(T_{max})$ in rabbits were 1 hr for oral administration, 1.5-2.5 hr for WIT-TWE, WIT-SLS, PEG, and WIT bases, and 2.5-4.0 hr for WIT-HOLL and WIT-CAP bases, but $T_{max}$ in humans were 1 hr for oral administration and WIT-TWE base, and 2-4 hr for WIT and WIT-HOLL bases. 4) Relative bioavailability (RBA) of aspirin suppositories in rabbits was higher in WIT-SLS, WIT-TWE and PEG bases than that in oral administration, and RBA of aspirin suppositories in humans was higher in the order of WIT-TWE >PEG >WIT-HOLL >oral >WIT bases tested. 5) Good correlation between dissolution rates and $C_{max}$ was obtained: y = 0.60x+32.23 (r = 0.96) for rabbits, and y = 0.60x+35.74 (r = 0.97) for humans.

• Journal of Pharmaceutical Investigation
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• 제25권1호
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• pp.19-29
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• 1995

The study was carried out to develop useful formulation for omeprazole(OMP) through OMP-ethylendiamine complex(OMPED), and the pharmaceutical properties of formula were tested to find out the difference in vivo behaviors of formulations between the free and complexed OMP. Oral and suppository dosage forms were also formulated and the dissolution profiles and pharmacokinetic parameters were measured to observe the difference in bioavailability between the free and complex form, and the correlation between dissolution rate and bioavailability was evaluated. The results are summarized as follows; In the case of formulation for oral administration, the release of OMP from enteric OMPED pellets was found satisfactory to the requirement standard and no decomposition of OMP in the pellets was found in acidic solution. Therefore the enteric OMPED pellets are anticipated to be a stable formulation. The release of OMP from OMPED tablet with chitosan as excipient and coated with cellulose acetate phthalate was found to be significantly retarded. The results of bioavailability test for OMP and OMPED tablets with lactose-excipient showed that the AUC value of OMP tablet was $116.89\;{\mu}g\;{\cdot}\;min/ml$, that of OMPED tablet was $161.10\;{\mu}g\;{\cdot}\;min/ml$, respectively. The reason why was thought that OMP decomposes more readily in body than OMPED, and the AUC of the tablet with chitosan-excipient and coated with cellulose acetate phthalate was most enhanced. In the case of bioavailability for suppositories with OMP, $OMP-{\beta}\;-cyclodextrin$ complex and OMPED, the AUC of OMPED suppository was most increased. From the above results, it is thought that the more stable and bioavailable oral or rectal dosage forms could be developed by using the OMPED as a potential OMP complex.

• Biomolecules & Therapeutics
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• 제22권1호
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• pp.78-81
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• 2014

Irinotecan suppository was prepared using the moulding method with a homogeneous blend. A sensitive and specific fluorescence method was developed and validated for the determination of irinotecan in plasma using HPLC. The pharmacokinetics of intravenous administered and rectal administered in rabbits was investigated. Following a single intravenous dose of irinotecan (50 mg/kg), the plasma irinotecan concentration demonstrated a bi-exponential decay, with a rapid decline over 15 min. $C_{max}$, $t_{1/2}$, $AUC_{0-30h}$ and $AUC_{0-{\infty}}$ were $16.1{\pm}2.7g/ml$, $7.6{\pm}1.2h$, $71.3{\pm}8.8{\mu}g{\cdot}h/ml$ and $82.3{\pm}9.5{\mu}g{\cdot}h/ml$, respectively. Following rectal administration of 100 mg/kg irinotecan, the plasma irinotecan concentration reached a peak of $5.3{\pm}2.5{\mu}g/ml$ at 4 h. The $AUC_{0-30h}$ and $AUC_{0-{\infty}}$ were $32.2{\pm}6.2{\mu}g{\cdot}h/ml$ and $41.6{\pm}7.2{\mu}g{\cdot}h/ml$, respectively. It representing ~50.6% of the absolute bioavailability.

• Biomolecules & Therapeutics
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• 제8권4호
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• pp.318-324
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• 2000

We have examined inhibitory erects on gasritis using omeprazole-cholestyramine resinate, which has been developed to increase the stability of omeprazole, the well-known proton pump inhibitor, in an acidic condition. To test the pharmacological action of this, we investigated the effect of omeprazole-cholestyramine resinate on indomethacin-induced gastritis in rats. Omeprazole was used as a reference drug. Orally administered omeprazole-cholestyramine resinate inhibited the indomethacin-induced gastritis in a dose-dependent manner. The inhibitory effect of omeprazole-cholestyramine resinate on the gastritis was similar to that of reference drug. In addition, rectal adminstration of the omeprazole-cholestyramine resinate inhibited the indomethacin-induced gastritis in a dose-dependent manner. The inhibitory effect of omeprazole-cholestyramine resinate was equipotent to reference drug. The basal gastric acid secretion was decreased when it was administered either orally or rectally. This inhibition of omfprazole-cholestyramine resinate was similar to that of omeprazole. These data suggest that omeprazole-cholestyramine resinate inhibit the gastritis in rats, and are comparable to omeprazole available in market.

• Parasites, Hosts and Diseases
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• 제40권1호
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• pp.1-7
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• 2002

The purpose of treatment for uncomplicated malaria is to produce a radical cute using the combination of: artesunate (4 mg/kg/day) plus mefloquine (8 mg/kg/day) for 3 days; a fixed dose of artemether and lumefantrine (20/120 mg tablet) named $Coartem^{\circledR}$ (4 tablets twice a day for three days for adults weighing more than 35 kg); quinine 10 mg/kg 8-hourly plus tetracycline 250 mg 6-hourly for 7 days (or doxycycline 200 mg as an alternative to tetracycline once a day for 7 days) in patients aged 8 years and over; $Malarone^{\circledR}$ (in adult 4 tablets daily for 3 days). In treating severe malaria, early diagnosis and treatment with a potent antimalarial drug is recommended to save the patient's life. The antimalarial drugs of choice are: intravenous quinine or a parenteral form of an artemisinin derivative (artesunate i.v./i.m. for 2.4 mg/kg followed by 1.2 mg/kg injection at 12 and 24 hr and then daily for 5 days; artemether i.m. 3.2 mg/kg injection followed by 1.6 mg/kg at 12 and 24 hrs and then dialy for 5 days; arteether i. m. ($Artemotil^{\circledR}$) with the same dose of artemether or artesunate suppository (5 mg/kg) given rectally 12 hourly for 3 days. Oral arlemisinin derivatives (artesunate, artemether, and dihydroartemisinin with 4 mg/kg/day) could replace parenteral forms when patients can tolerate oral medication. Oral mefloquine (25 mg/kg divided into two doses 8 hrs apart) should be given at the end of the artemisinin treatment course to reduce recrudescence.