Thirteen-week study

Many antiviral agents, particularly some anti-HIV agents, have rather short plasma half-lives, which require frequent oral administration of the agent. Thirteen-week studies have been conducted with t.i.d. dosing of rats and monkeys, requiring around-the-clock shift work for technical staff of the laboratory. 

Histopathologic lesions of the liver have been demonstrated in several oral studies in rodents dosed at higher levels of 1,4-dichlorobenzene. Cloudy swelling and centrilobular necrosis were observed in the livers of rats that received 1,4-dichlorobenzene at 500 mg/kg/day for 4 weeks (Hollingsworth et al. 1956). Thirteen-week studies have resulted in degeneration and necrosis of hepatocytes in rats that received doses of 1,200 mg/kg/day and above and in mice, hepatocellular degeneration was observed at... 

Dunnick JK, Graham DG, Yang RS, etal. 1989. Thirteen-week toxicity study of w-hcxanc in B6C3F1 mice after inhalation exposure. Toxicology 57(2) 163-172. 

Pyramid or — rolling acute and/or two or four week study Thirteen — weeks in two species Tolerance, PK -> and efficacy with human dosing up to one month in length DELAY — ... 

When one is scheduling out an entire testing program on contract, it should be noted that, if multiple tiers of tests are to be performed (such as acute, two-week, thirteen-week, and lifetime studies), then these must be conducted sequentially, as the answer from each study in the series defines the design and sets the doses for the subsequent study. 

Nitschke KD, Kociba RJ, Keyes DG, et al. 1981. A thirteen week repeated inhalation study of ethylene dibromide in rats. Fundam AppI Toxicol 1 437-442. 

Tegeris AS, Balmer MF, Gamer FM, et al A thirteen week skin irritation study with acrylic acid in three strains of mice. Abst no.504 Toxicologist 8 504, 1988. 

Thirteen-week toxicity studies of 2,2-bis(bromomethyl)propane-l,3-diol were conducted in male and female Fischer 344/N rats and B6C3Fi mice to determine target organ toxicity. 2,2-Bis(bromomethyl)propane-l,3-diol (technical grade, 78.6% pure) was administered by gavage in com oil for five days per week to rats, 6-7 weeks of age, at doses of 0, 50, 100, 200, 400 or 800 mg/kg bw and to mice, 6-9 weeks of age. 

IRDC. 1977. Octabromodiphenyl ether. Thirteen week feeding study in rats. International Research and Development Corporation. Submitted to U.S. EPA under TSCA Section 8D, Fiche no. OTS0522297. 

Lina, B., Korte, H., Nyman, L., and Unkila, M. 2005. A thirteen week dietary toxicity study with 7-hydroxsymatairesinol potassium acetate (HMR lignan) in rats. Regul. Toxicol. Pharmacol. 41, 28-38. 

Mellert, W., Deckardt, K., Gembardt, C., Schulte, S., and Van Ravenzwaay, B. 2002. Thirteen-week oral toxicity study of synthetic lycopene products in rats. Food Chem. Toxicol 40, 1581-1588. 

Parker, R.M., Crowell, J.A., Bucci, T.J., Thurman, J.D., Dacre, J.C. (1990). Thirteen-week oral toxicity studies of tahun (GA) using CD rats. Toxicologist 10 343. 

Levine BS, Furedi EM, Gordon DE, et al. 1981. Thirteen-week toxicity study of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) in Fischer 344 rats. Toxicol Lett 8 241-245. 

The qualitative and quantitative patterns of alkaloid content in the various organs of Lupinus termis Forsk., one of three Lupinus species indigenous to Egypt, have been studied. The maximum alkaloid content was observed in the seeds of very ripe fruits thirteen weeks after flowering at the same time the alkaloid content of the roots was at its minimum. Thin-layer chromatography provided evidence for the presence of nine alkaloids, of which the major one was identified as (+)-lupanine. A second alkaloid was reported to show the same chromatographic behaviour as 13-hydroxylupanine, but was not positively identified. This work confirms an earlier report d of the presence of these two alkaloids in Lebanese specimens of L. termis. 

Muto, T., T. Watanabe, M. Okamura, et aL 2003. Thirteen-week repeated dose toxicity study of wormwood (Artemisia absinthium) extract in rats. J. Toxicol. Sci. 28(5) 471-478. 

Hagiwara, A., N. Imai, T. Ichihara, et al. 2003. A thirteen-week oral toxicity study of annatto extract (norbixin), a natural food color extracted from the seed coat of annatto (Bixa orellana L.), in Sprague-Dawley rats. Food Chem. Toxicol. 41(8) 1157-1164. 

Mondino, A., Peano, S. Berruto, P. (1981) Thirteen week repeated dose study of the test article TT191 (3-methyi-1,2,4-trithiane) orally administered to Sprague-Dawley Charles River CD(SD)BR rats. Unpublished report from Istituto di Ricerche Biomediche Antoine Marxef SpA, Torino, Italy. Submitted to WHO by the International Organization of the Flavor Industry, Brussels, Belgium. 

Robinul 2 mg was administered orally to a total of 34 subjects. Thirteen subjects had gout and had received no hypouricemic therapy for 2 weeks prior to the study. Six subjects had borderline or definite asymptomatic hyperuricemia with serum urate values ranging from 6.7 to 7.1 mg%. The remaining 15 subjects were normouricemic with serum urate values ranging from 3.3 to 6.2 mg%. Care was taken... 

Bi-level NIV may be used as a first-line treatment, with supplemental oxygen (27). Expiratory airway pressure is titrated to control h5q)opneas and apneas, and inspiratory airway pressure is added to control Paco2. If bi-level NIV fails, nasal volume ventilation may be used (29). In many patients with OHS and predominant OSA, once hypercapnia has improved (which may take several weeks) nCPAP may be used (29). Thirteen obese patients (n = 13) with a BMI > 35, aged 28-69 years with severe OSAS and hypercapnia (8.2 0.3 kPa) and failing to respond to initial CPAP therapy, were treated via a nasal nocturnal volume-cycled ventilator, which was tolerated by all patients. Significant improvements in daytime arterial blood gas levels were obtained after 7 to 18 days of nasal intermittent positive pressure ventilation (29) in 10 of the 13 patients three months later, 12 of the 13 patients could be converted to nCPAP therapy and one patient remained on NIV. In another study (37), the same results were observed after three months of home nocturnal bi-level NIV in seven patients, three of whom had severe obesity. 

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