• Journal of Pharmaceutical Investigation
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• 제32권1호
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• pp.47-54
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• 2002

Cimetropium bromide, a quaternary ammonium compound which is chemically related to scopolamine, exhibits its antispasmodic activity by competing with acetylcholine for the muscarinic receptors of the smooth muscle of gastrointestinal tract. The drug has been used for the treatment of various disorders involving spasms of the musculature of the gastrointestinal, biliary and genitourinary tracts. The purpose of the present study was to evaluate the bioequivalence of two cimetropium bromide tablets, $Algiron^{TM}$ (Boehringer Ingelheim Korea Ltd.) and $Alpit^{TM}$ (Hana Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The cimetropium bromide release from the two cimetropium bromide tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty normal male volunteers, $25.25{\pm}2.10$ years in age and $65.76{\pm}6.39$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three tablets containing 50 mg of cimetropium bromide per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of cimetropium bromide in serum were determined using HPLC method with UV detector. The dissolution profiles of two cimetropium bromide tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t,\;C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t\;and\;C_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the $Algiron^{TM}$ were 2.19%, -5.97% and 3.49%, respectively. Minimum detectable differences $({\Delta})\;at \;{\alpha}=0.05\;and\;1-{\beta}=0.8$ were less than 20% (e.g., 13.71 %, 19.05% and 15.11% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The powers $(1-{\beta})\;at\;{\alpha}=0.05,\;{\Delta}=0.2\;for\;AUC_t$, $C_{max}\;and\;T_{max}$ were 97.79%, 83.22% and 95.60%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.84{\sim}10.21,\;-17.11{\sim}5.18\;and\;-5.35{\sim}12.33\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t\;and\;C_{max}$. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.94{\sim}1.10\;and\;0.85{\sim}1.05\;for\;AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Alpit^{TM}$ tablet is bioequivalent to $Algiron^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제20권4호
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• pp.223-228
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• 1990

The contribution of endogenous transport systems to the blood-brain barrier (BBB) transport of basic and acidic drugs was studied by using a carotid injection technique in rats and an isolated bovine cerebrovascular disease state were compared between the normotensive rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) which have been well established as an animal model with pathogenic similarities to humans. Basic drugs such as eperisone, thiamine and scopolamine inhibited, in a concentration dependent manner the in vivo uptake of $[{^3}H]choline$ through BBB, whereas amino acids and acidic drugs such as salicylic acid and valproic acid did not inhibit the uptake. The uptake of $[^3H]choline$ by B-CAP increased with time and showed a remarkable temperature dependency. The uptake of $[^3H]choline$ by B-CAP showed the very similar inhibitory effects as observed in the in vivo brain uptake, and was competitively inhibited by a basic drug, eperisone. The in vivo BBB uptakes of $[^3H]acetic$ acid and $[^{14}C]salicylic$ acid were dependent on pH of the injectate and the concentration of drugs. Several acidic drugs such such as salicylic acid, benzoic acid and valproic acid inhibited the in vivo uptake of $[^3H]acetic$ acid, whereas amino acid, choline and a basic drug such as eperisone did not inhibit the uptake. The uptake of acetic acid by B-CAP was competitively inhibited by salicylic acid. The permeability surface area product (PS) through BBB for $[^3H]choline$ in SHRSP was significantly lower than that in WKY. The concentration of choline in the brain dialysate in SHRSP was about half of that in WKY, while no significant difference was observed in the plasma concentration of choline between SHRSP and WKY. No significant difference was observed in the transport of monocarboxylic acids, glucose and neutral amino acid through BBB between SHRSP and WKY. From these results, it was concluded that BBB transport system of choline contributes to the transport of basic drugs through BBB, that acidic drugs can be transported via a moncarboxylic acid BBB transport system and that the specific dysfuntion of the BBB choline transport in SHRSP was ascribed to the reduction of the maximum velocity of choline concentration in the brain interstitial fluids.

• Korean Journal of Radiology
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• 제24권11호
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• pp.1093-1101
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• 2023

Objective: Cine magnetic resonance imaging (MRI) has emerged as a noninvasive method to quantitatively assess bowel motility. However, its accuracy in measuring various degrees of small bowel motility has not been extensively evaluated. We aimed to draw a quantitative small bowel motility score from cine MRI and evaluate its performance in a population with varying degrees of small bowel motility. Materials and Methods: A total of 174 participants (28.5 ± 7.6 years; 135 males) underwent a 22-second-long cine MRI sequence (2-dimensional balanced turbo-field echo; 0.5 seconds per image) approximately 5 minutes after being intravenously administered 10 mg of scopolamine-N-butyl bromide to deliberately create diverse degrees of small bowel motility. In a manually segmented area of the small bowel, motility was automatically quantified using a nonrigid registration and calculated as a quantitative motility score. The mean value (MV) of motility grades visually assessed by two radiologists was used as a reference standard. The quantitative motility score's correlation (Spearman's ρ) with the reference standard and performance (area under the receiver operating characteristics curve [AUROC], sensitivity, and specificity) for diagnosing adynamic small bowel (MV of 1) were evaluated. Results: For the MV of the quantitative motility scores at grades 1, 1.5, 2, 2.5, and 3, the mean ± standard deviation values were 0.019 ± 0.003, 0.027 ± 0.010, 0.033 ± 0.008, 0.032 ± 0.009, and 0.043 ± 0.013, respectively. There was a significant positive correlation between the quantitative motility score and the MV (ρ = 0.531, P < 0.001). The AUROC value for diagnosing a MV of 1 (i.e., adynamic small bowel) was 0.953 (95% confidence interval, 0.923-0.984). Moreover, the optimal cutoff for the quantitative motility score was 0.024, with a sensitivity of 100% (15/15) and specificity of 89.9% (143/159). Conclusion: The quantitative motility score calculated from a cine MRI enables diagnosis of an adynamic small bowel, and potentially discerns various degrees of bowel motility.