Seizi Oga

Pharmacokinetic profile and adverse gastric effect of zinc-piroxicam in rats.

Complexation of piroxicam with zinc extends its absorption time in rats. The time of peak concentration value for complexed piroxicam was 5.27 hr compared to only 2.56 hr for the uncomplexed agent. Piroxicam and zinc-piroxicam show similar inhibitory effects on carrageenin-induced paw edema. Zinc-piroxicam is less irritating than piroxicam on the gastric mucosa.

Pharmacokinetic profile of piroxicam β-cyclodextrin, in rat plasma and lymph☆

Abstract 1. 1. The absorption of piroxicam into the blood of rats is significantly slower after oral administration of piroxicam β-cyclodextrin than of free piroxicam. 2. 2. The pharmacokinetic profiles of piroxicam in rat lymph were very similar in both groups. 3. 3. Bioavailability of piroxicam in plasma is higher after treatment with the inclusion product than with free piroxicam. On the other hand, bioavailability in lymph is higher when free piroxicam is administered.

Effect of Pfaffia iresinoides on the experimental inflammatory process in rats

Antiinflammatory activities of aqueous and saponin extracts and ecdysterone obtained from Pfaffia iresinoides (Sprengel) were studied by using three experimental inflammatory models in rats. The saponin extract (25 and 50 mg/kg, p.o.) reduced the leukocyte migration, particularly of mononuclear cells in the carrageenin‐induced pleurisy. It also inhibited the granuloma tissue formation following cotton pellet implantation and the complete Freunds adjuvant‐induced arthritis. The aqueous extract, in the same conditions, was effective on both carrageenin‐induced pleurisy and complete Freunds adjuvant arthritis. However, it did not alter the granuloma formation. The ecdysterone (5 mg/kg, p.o.), isolated from P. iresinoides, showed no effect on these inflammatory processes.

Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats

We investigated the anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex (5.5 or 11 mg/kg) in male Wistar rats (180-300 g, N = 6) and compared it to free diclofenac (5 or 10 mg/kg) and to the combination of diclofenac (5 or 10 mg/kg) and zinc acetate (1.68 or 3.5 mg/kg). The carrageenin-induced paw edema and the cotton pellet-induced granulomatous tissue formation models were used to assess the anti-inflammatory activity, and the Hargreaves model of thermal hyperalgesia was used to assess the antinociceptive activity. To investigate the effect of orally or intraperitoneally (ip) administered drugs on cold-induced gastric lesions, single doses were administered before exposing the animals to a freezer (-18 degrees C) for 45 min in individual cages. We also evaluated the gastric lesions induced by multiple doses of the drugs. Diclofenac plus zinc complex had the same anti-inflammatory and antinociceptive effects as diclofenac alone. Gastric lesions induced by a single dose administered per os and ip were reduced in the group treated with zinc-diclofenac when compared to the groups treated with free diclofenac or diclofenac plus zinc acetate. In the multiple dose treatment, the complex induced a lower number of the most severe lesions when compared to free diclofenac and diclofenac plus zinc acetate. In conclusion, the present study demonstrates that the zinc-diclofenac complex may represent an important therapeutic alternative for the treatment of rheumatic and inflammatory conditions, as its use may be associated with a reduced incidence of gastric lesions.

Clinical and laboratory parameters in dapsone acute intoxication

OBJECTIVE To determine the severity of dapsone (DDS) acute intoxication - an uncommon medical event - using clinical and laboratory parameters. METHODS Two hundred and seventy four patients with acute DDS intoxication, aged 1 month to 50 years old, were studied and classified into four age groups. Clinical evaluation was assessed through a protocol and correlated with laboratory parameters. Spectrophotometric methods were used to analyze methemoglobinemia (MHbp) and dapsonemia (DDSp). RESULTS The most prevalent clinical sign of intoxication was cyanosis, seen in 65.7% of the patients and in 100% of children less than 5 years of age. According to laboratory criteria, MHbp-related severe clinical intoxication was seen in 56.2% and DDSp-related occurred in 58% of the patients. Regarding DDSp, intoxication was considered severe when 20 tablets (100 mg each) were ingested, a median of 29 microg/ml. Regarding MHbp, intoxication was severe when 7.5 tablets were ingested, a median of 38% of the total Hb. The correlation between MHbp and DDSp was statistically significant (n=144, r=0.32, p<0.05). Negative correlation was observed between MHbp and the time elapsed since DDS intake (n=124, r=-0.34, p<0.001). There was also a negative correlation between DDSp and the time elapsed since DDS intake (n=63, r=-0.35, p<0.0001). CONCLUSIONS Longitudinal analysis showed a significant association between methemoglobinemia and the time elapsed after the intake (t), according to the equation: Dapsonemia = 12.9256 - 0.0682t + 0.234 methemoglobinemia

Anti-Inflammatory Activity and Gastric Lesions Induced by Zinc-Tenoxicam

Oral administration of tenoxicam or zinc-tenoxicam complex inhibited to a similar extent carrageenin-induced paw oedema and granulomatous tissue formation in rats as well as the acetic acid induced writhing response in mice. Gastric lesions induced by oral administration of zinc-tenoxicam were reduced in number and severity when compared with those induced by tenoxicam or the co-administration of tenoxicam and zinc acetate. However, after intraperitoneal administration, both zinc-tenoxicam and tenoxicam plus zinc acetate induced a reduced number of gastric lesions as compared with tenoxicam.

Inhibitory effects of beryllium chloride on rat liver microsomal enzymes.

A single i.v. dose (0.1 mmol Be2+/kg) of beryllium chloride prolonged the duration of pentobarbital-induced sleep and zoxazolamine-induced paralysis, in rats. The effects are correlated with changes of the pharmacokinetic parameters and with the in vitro inhibition of both aliphatic and aromatic hydroxylation of pentobarbital and zoxazolamine. In vitro N-demethylation of meperidine and aminopyrine was partially inhibited while O-demethylation of quinidine was unaffected by liver microsomes of rats pretreated with beryllium salt. The findings give clues that beryllium chloride inhibits some forms of cytochrome P-450, especially those responsible for hydroxylation of substrates, like pentobarbital and zoxazolamine.

Effect of piroxicam β-cyclodextrin complex on experimental inflammation

Abstract 1. 1. The effectiveness of the inclusion product of piroxicam with β-cyclodextrin was compared to that of free piroxicam on inflammatory reactions by using three experimental inflammatory models in rats. 2. 2. The inclusion compound showed anti-inflammatory effects similar to those of simple piroxicam on granuloma tissue formation and arthritis induced by complete Freund adjuvant. 3. 3. In carrageenin-induced pleurisy, the piroxicam β-cyclodextrin reduced leukocyte mobilization more intensely than non-complexed piroxicam. 4. 4. These results suggest that β-cyclodextrin is a useful tool for improving the efficacy of piroxicam.

Propylene glycol enhances anti-inflammatory effects of phenylbutazone

1. The interference of propylene glycol with anti-inflammatory effects of phenylbutazone was investigated. 2. Inhibitory effect of phenylbutazone on both carrageenin-induced edema and the cotton pellet granuloma was increased when propylene glycol was used as solvent. 3. Propylene glycol given alone inhibited carrageenin-induced edema and pleurisy, as well as granulomatous tissue formation. 4. Some pharmacokinetic parameters of phenylbutazone were also changed by propylene glycol administered simultaneously. 5. These results suggest that propylene glycol probably increases the anti-inflammatory effect of phenylbutazone by summation and by raising the plasma half-life and the distribution volume of phenylbutazone.

Acute and subacute toxicity of Cochlospermum regium (Mart. & Schr.) Pilger.

The toxicity of a hydroethanol extract of the subterranean part of Cochlospermum regium was evaluated in mice and rats. The extract had moderate acute toxicity when administered intraperitoneally and low toxicity upon oral administration. A subacute toxicity test revealed that the extract is well tolerated by these animals. Copyright