Increased bioavailability of clomipramine after sublingual administration in rats

Yoo, Sun Dong; Yoon, Byung Mun; Lee, Hye Suk; Lee, Kang Choon

doi:10.1021/js990163p

Cited by 33 publications

(5 citation statements)

References 11 publications

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“…The isobologram of this combination showed a synergic antitrypomastigote effect, evi- denced by a CI of Ͻ1 (CI, 0.375). These data, together with the pharmacokinetic parameters of the drugs (32,33) and mouse total volume of circulating blood, allow us to anticipate that BZ doses could be reduced to 25% of the clinically recommended concentration (100 mg/kg/day) when combined with 7.5 mg/kg/day of CMP. The checkerboard strategy was employed to test the capacities of other compounds to interact with BZ and whether these interactions could increase its trypanocidal activity (41,42).…”

Section: Discussionmentioning

confidence: 99%

Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease

García

Ponce

Sanmarco

et al. 2016

Antimicrob Agents Chemother

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bChagas disease is an important public health problem in Latin America, and its treatment by chemotherapy with benznidazole (BZ) or nifurtimox remains unsatisfactory. In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated the in vitro and in vivo anti-Trypanosoma cruzi effects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ. In vitro studies, carried out using a checkerboard technique on trypomastigotes (T. cruzi strain Tulahuen), revealed a combination index (CI) of 0.375, indicative of a synergistic effect of the drug combination. This result was correlated with the data obtained in infected BALB/c mice. We observed that during the acute phase (15 days postinfection [dpi]), BZ at 25 mg/kg of body weight/day alone decreased the levels of parasitemia compared with those of the control group, but when BZ was administered with CMP, the drug combination completely suppressed the parasitemia due to the observed synergistic effect. Furthermore, in the chronic phase (90 dpi), mice treated with both drugs showed less heart damage as assessed by the histopathological analysis, index of myocardial inflammation, and levels of heart injury biochemical markers than mice treated with BZ alone at the reference dose (100 mg/kg/day). Collectively, these data support the notion that CMP combined with low doses of BZ diminishes cardiac damage and inflammation during the chronic phase of cardiomyopathy. The synergistic activity of BZ-CMP clearly suggests a potential drug combination for Chagas disease treatment, which would allow a reduction of the effective dose of BZ and an increase in therapeutic safety.

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Section: Discussionmentioning

confidence: 99%

Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease

García

Ponce

Sanmarco

et al. 2016

Antimicrob Agents Chemother

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“…This group of animals were implanted with 2 mm non-functional, single shank neural probes instead of functional neural probes since electrophysiology metrics would not be evaluated here. There were four animals per group (N = 4) for the following four time points: 1 week, 2 weeks, 4 weeks, and 6 weeks [45][46][47][48].…”

Section: Bioavailability Surgerymentioning

confidence: 99%

Investigation of the Feasibility of Ventricular Delivery of Resveratrol to the Microelectrode Tissue Interface

et al. 2021

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(1) Background: Intracortical microelectrodes (IMEs) are essential to basic brain research and clinical brain–machine interfacing applications. However, the foreign body response to IMEs results in chronic inflammation and an increase in levels of reactive oxygen and nitrogen species (ROS/RNS). The current study builds on our previous work, by testing a new delivery method of a promising antioxidant as a means of extending intracortical microelectrodes performance. While resveratrol has shown efficacy in improving tissue response, chronic delivery has proven difficult because of its low solubility in water and low bioavailability due to extensive first pass metabolism. (2) Methods: Investigation of an intraventricular delivery of resveratrol in rats was performed herein to circumvent bioavailability hurdles of resveratrol delivery to the brain. (3) Results: Intraventricular delivery of resveratrol in rats delivered resveratrol to the electrode interface. However, intraventricular delivery did not have a significant impact on electrophysiological recordings over the six-week study. Histological findings indicated that rats receiving intraventricular delivery of resveratrol had a decrease of oxidative stress, yet other biomarkers of inflammation were found to be not significantly different from control groups. However, investigation of the bioavailability of resveratrol indicated a decrease in resveratrol accumulation in the brain with time coupled with inconsistent drug elution from the cannulas. Further inspection showed that there may be tissue or cellular debris clogging the cannulas, resulting in variable elution, which may have impacted the results of the study. (4) Conclusions: These results indicate that the intraventricular delivery approach described herein needs further optimization, or may not be well suited for this application.

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“…30 CDs enhance the mucosal drug permeability mainly by increasing the free drug availability at the absorptive surface. 127,128 CD complexation can provide better and uniform absorption of low-soluble drugs with poor and erratic absorption 91 and also enhance the drug activity on oral administration 123,125,126 CD complexation increased the anthelmentic activity of albendazole and provided a high plasma concentration of the active metabolite. 133 CD complexation increased the absorption of poorly water-soluble ↑, increased effect drugs, delivered via buccal or sublingual mucosa.…”

Section: Applications In Drug Deliverymentioning

confidence: 99%

Cyclodextrins in drug delivery: An updated review

et al. 2005

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The purpose of this review is to discuss and summarize some of the interesting findings and applications of cyclodextrins (CDs) and their derivatives in different areas of drug delivery, particularly in protein and peptide drug delivery and gene delivery. The article highlights important CD applications in the design of various novel delivery systems like liposomes, microspheres, microcapsules, and nanoparticles. In addition to their well-known effects on drug solubility and dissolution, bioavailability, safety, and stability, their use as excipients in drug formulation are also discussed in this article. The article also focuses on various factors influencing inclusion complex formation because an understanding of the same is necessary for proper handling of these versatile materials. Some important considerations in selecting CDs in drug formulation such as their commercial availability, regulatory status, and patent status are also summarized. CDs, because of their continuing ability to find several novel applications in drug delivery, are expected to solve many problems associated with the delivery of different novel drugs through different delivery routes.

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Increased bioavailability of clomipramine after sublingual administration in rats

Cited by 33 publications

References 11 publications

Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease

Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease

Investigation of the Feasibility of Ventricular Delivery of Resveratrol to the Microelectrode Tissue Interface

Cyclodextrins in drug delivery: An updated review

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