Bioequivalence study between a fixed-dose single-pill formulation of nebivolol plus hydrochlorothiazide and separate formulations in healthy subjects using high-performance liquid chromatography coupled to tandem mass spectrometry.

Systemic arterial hypertension is a major risk factor for cerebrovascular disease. Therefore, adequate control of blood pressure is of enormous importance. One of the many fixed-dose single-pill antihypertensive formulations available on the market is the combination of nebivolol and hydrochlorothiazide. The objective of this study was to develop two distinct high-performance liquid chromatography coupled to tandem mass spectrometry methods to simultaneously quantify nebivolol and hydrochlorothiazide in human plasma. The methods were employed in a bioequivalence study, the first assay involving a nebivolol fixed-dose single-pill formulation based on healthy Brazilian volunteers. Nebilet HCT™ (nebivolol 5 mg + hydrochlorothiazide 12.5 mg tablet, manufactured by Menarini) was the test formulation. The reference formulations were Nebilet™ (nebivolol 5 mg tablet, manufactured by Menarini) and Clorana™ (hydrochlorothiazide 25 mg tablet, manufactured by Sanofi). For both analytes, liquid-liquid extraction was employed for sample preparation and the chromatographic run time was 3.5 min. The limits of quantification validated were 0.02 ng/mL for nebivolol and 1 ng/mL for hydrochlorothiazide. Since the 90% CI for Cmax , AUC(0-last) and AUC(0-inf) individual test/reference ratios were within the 80-125% interval indicative of bioequivalence, it was concluded that Nebilet HCT™ is bioequivalent to Nebilet™ and Clorana™.

Anti-nociceptive, anti-hyperalgesic and anti-arthritic activity of amides and extract obtained from Piper amalago in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine. AIM OF THE STUDY: This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models. MATERIALS AND METHODS: Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg). RESULTS: Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test. CONCLUSION: The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The amides obtained seemed to be the active component(s) present in the EEPA because they proved to be anti-nociceptive and anti-hyperalgesic in models of acute pain. Considering that few drugs are currently available for the treatment of chronic pain, especially neuropathic pain, the present results may have clinical relevance and open new possibilities for the development of new anti-hyperalgesic and anti-arthritic agents from P. amalago.

Diuretic and Anti-Inflammatory Activities of the Microencapsulated Acrocomia aculeata (Arecaceae) Oil on Wistar Rats.

Acrocomia aculeata, popularly known as "bocaiuva," is widely acknowledged in culinary and traditional medicines to treat cardiovascular diseases, a combined effect with diuretics that are also used for hypertension. However, there are no scientific data published to support its use as functional food and its ethnopharmacological use. This study intended to determine the composition of fatty acids of the pulp oil and evaluate the diuretic action and anti-inflammatory activity of the in natura and microencapsulated oil orally administrated on rats. The obtained results confirm the prevalence of monounsaturated fatty acids (68.51%), especially oleic acid (65.68%±1.05%), in the oil from the bocaiuva pulp. The in natura A. aculeata oil has diuretic (P<.01) and anti-inflammatory potential, which promoted a marked inhibition on the hind paw edema induced by carrageenan (67%±7% after 2 h) (P<.01). In addition, results show that the oral administration of the bocaiuva oil at 300 (P<.05) and 700 (P<.05) mg/kg doses significantly inhibited the leukocyte migration induced by carrageenan to the pleural cavity in rats. The inhibitions equaled 91%±3% and 81%±16%, respectively. The microencapsulated oil also showed antiedematogenic (P<.01) as well as diuretic activities (P<.01). The microencapsulation by complex coacervation was shown to be a technique that favors the bioavailability and preservation of bioactive components of the bocaiuva oil.