An unusual case of carbamazepine poisoning with a near-fatal relapse after two days.

A severe case of carbamazepine is described in which the drug and its major metabolite were monitored by means of HPLC. After 2 days of treatment a dramatic rise in plasma concentration of carbamazepine and its metabolite was observed, accompanied by a relapse into deep coma, then followed by a rapid elimination of the drugs and complete recovery within 4 days. The possible mechanisms underlying these phenomena and potential therapeutic measures are discussed.     

Comparison of hospitalization rates in patients with community-acquired pneumonia treated with telithromycin for 5 or 7 days or clarithromycin for 10 days

SUMMARY

Aims: To compare the impact on hospitalization rates and the clinical efficacy of oral telithromycin and clarithromycin treatment in patients with community-acquired pneumonia (CAP).

Methods: A total of 581 patients with CAP were enrolled in this randomized, double-blind, parallel-group, multinational study, of whom 575 were evaluated for healthcare resource utilization from a payer perspective (intent to treat [ITT] population). Patients received telithromycin 800?mg once daily for 5 (n?=?193) or 7 (n?=?195) days, or clarithromycin 500?mg once daily for 10days (n?=?187). The primary efficacy endpoint was clinical outcome at test of cure (Days 17–24) in the per-protocol population. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use were compared by treatment group (ITT) up to late post-therapy (Days 31-36). Study investigators blinded to treatment assessed whether hospital admissions were CAP-related or not. CAP-related

hospitalization costs (US$) for telithromycin and clarithromycin were compared.

Results: Clinical cure rates were similar in patients who received clarithromycin for 10days and telithromycin for 5 or 7 days: 91.8% (134/146), 89.3% (142/159), and 88.8% (143/161), respectively, and both 5- and 7-day telithromycin were statistically equivalent to clarithromycin (difference: ?2.5 and ?3.0%, respectively; 95% CI: ?9.7, 4.7 and ?10.2, 4.3, respectively). There were 7 CAP-related hospital admissions among clarithromycin patients vs 3 (p?=?0.283) and 1 (p?=?0.021) admissions among 5- and 7-day telithromycin patients, respectively. The number of hospital days/100 patients was 40.1 for clarithromycin vs 17.1 and 7.2 for 5- and 7-day telithromycin, respectively. Projected hospitalization costs/100 patients were $86205 for clarithromycin vs $37930 (difference: ?26446; 95% CI: ?66654; 13762) and $16 091 (difference: ?37847; 95% CI: ?77953; 2259) for 5- and 7-day telithromycin, respectively.

Conclusions: Data from this study demonstrate that telithromycin 800?mg once daily for 5 or 7 days is an effective treatment for CAP, and that telithromycin treatment of CAP may be associated with fewer hospital days and potentially lower hospitalization costs than clarithromycin treatment.     

Comparison of hospitalization rates in patients with community-acquired pneumonia treated with telithromycin for 5 or 7 days or clarithromycin for 10 days

AIMS: To compare the impact on hospitalization rates and the clinical efficacy of oral telithromycin and clarithromycin treatment in patients with community-acquired pneumonia (CAP). METHODS: A total of 581 patients with CAP were enrolled in this randomized, double-blind, parallel group, multinational study, of whom 575 were evaluated for healthcare resource utilization from a payer perspective (intent to treat [ITT] population). Patients received telithromycin 800 mg once daily for 5 (n = 193) or 7 (n = 195)days, or clarithromycin 500 mg once daily for 10 days (n = 187). The primary efficacy endpoint was clinical outcome at test of cure (Days 17-24) in the per-protocol population. Frequency of CAP-related hospitalizations, physician visits/tests/procedures, and additional respiratory tract infection-related antibacterial use were compared by treatment group (ITT) up to late post- for clarithromycin vs dollars 37930 (difference: -26446; therapy (Days 31-36). Study investigators blinded to treatment assessed whether hospital admissions were CAP-related or not. CAP-related hospitalization costs (USdollars) for telithromycin and clarithromycin were compared. RESULTS: Clinical cure rates were similar in patients who received clarithromycin for 10 days and telithromycin for 5 or 7 days: 91.8% (134/146), 89.3% (142/159), and 88.8% (143/161), respectively, and both 5- and 7-day telithromycin were statistically equivalent to clarithromycin (difference: -2.5 and -3.0%, respectively; 95% CI: -9.7, 4.7 and -10.2, 4.3, respectively). There were 7 CAP-related hospital admissions among clarithromycin patients vs 3 (p = 0.283) and 1 (p = 0.021) admissions among 5- and 7-day telithromycin patients, respectively. The number of hospital days/100 patients was 40.1 for clarithromycin vs 17.1 and 7.2 for 5- and 7-day telithromycin, respectively. Projected hospitalization costs/100 patients were dollars 86205 95% CI: -66 654; 13 762) and dollars 16 091 (difference: -37 847; 95% CI: -77953; 2259) for 5- and 7-day telithromycin, respectively. CONCLUSIONS: Data from this study demonstrate that telithromycin 800 mg once daily for 5 or 7 days with fewer hospital days and potentially lower is an effective treatment for CAP,and that telithromycin treatment of CAP may be associated hospitalization costs than clarithromycin treatment.     

Excessive accumulation of hepatic copper in LEC rats aged 80 days without hepatitis and 130 days with hepatitis.

The Cu concentration was about 40 and 60 times higher in the liver in Long-Evans with a cinnamon-like coat color (LEC) rats aged 80 days (without hepatitis) and 130 days (with hepatitis), respectively than in the liver in Fischer rats. Most hepatic Cu was recovered in the cytosol fraction. Furthermore, about 96% and 84% of the cytosolic Cu was found in the metallothionein region on a Sephadex G-75 column in LEC rats aged 80 and 130 days, respectively. The hepatic metallothionein concentration was about 130 to 140 times higher in LEC rats than in Fischer rats when the concentration was expressed as metallothionein-bound Cu. Three forms of Cu-metallothionein were isolated by DEAE-cartridge. Although the concentration of hepatic Cu-metallothionein and its composition of polymorphic form were not changed greatly in hepatitis phase (in the 130-day-old LEC rats), activities of serum enzymes, aspartate aminotransferase (GOT) and alanine aminotransferase (GPT) were increased significantly. The LEC rat showed a significantly low concentration of biliary Cu and markedly low activity of ceruloplasmin (as ferroxidase). Serum Cu showed a low concentration in the 80-day-old LEC rats, but recovered to the control level in the 130-day-old LEC rats. The abnormal accumulation of Cu may be due to the inherent reduction of excretion of Cu into the bile and blood. Such deposition may be a trigger for the onset of the spontaneous hepatitis occurring at 90-120 days after birth and for the onset of hepatoma later.     

Cisplatin plus gemcitabine on days 1 and 4 every 21 days for solid tumors: Result of a dose-intensity study

Summary Background: Three and 4-week cisplatin-gemcitabine schedules have shown similar dose-intensity (DI) and activity in non-small-cell lung cancer (NSCLC). The 3-week schedule is generally preferred because it enables better treatment compliance. To improve DI and compliance further, we delivered gemcitabine plus cisplatin over 4 days every 21 days. Methods: Patients with any stage NSCLC or epithelial neoplasms and an ECOG PS ≤2 were given gemcitabine 1000 mg/m² on days 1 and 4 plus cisplatin 70 mg/m² on day 2 of a 21-day cycle. Minimax design was used and a received DI for gemcitabine of ≥580 mg/m²/wk was considered successful. Results: Thirty-nine patients (34 NSCLC, 5 epithelial neoplasias) were enrolled. SWOG grade 3–4 neutropenia and thrombocytopenia were observed in 17.9% and 12.8% of patients, respectively. Nonhematological toxicity was minimal. Twenty-eight (18%) of 158 cycles required dose modifications and/or delays. Twenty-five patients received a gemcitabine dose intensity of ≥580 mg/m²/wk. The received DIs were 601.8 mg/m²/wk for gemcitabine and 21.0 for cisplatin, with a relative DIs of 90.3% and 90.1%, respectively. The response rate of 27 evaluable patients with NSCLC was 44% (95% confidence interval [CI], 25.3 to 62.7%). Conclusions: The shorter schedule of gemcitabine on days 1 and 4 plus cisplatin on day 2 produces an effective DI and a toxicity profile comparable to that of weekly regimens.     

Investigation of HCB as a metabolite from female rats treated daily for six days with lindane

The biotransformation of lindane to hexachlorobenzene (HCB) by male rats was recently reported. Since HCB has been widely detected in human milk samples, and since the transplacental transfer of HCB to the fetus has been demonstrated in several species, the metabolism of lindane to HCB in female rats was investigated. Young adult female Fischer 344 rats were dosed p.o. with either 20 mg lindane/kg/day or an equivalent volume of the peanut oil vehicle. Feces samples were collected daily for two consecutive 4-hr intervals and a 16-hr interval. Twenty-four hours after the final treatment, all rats were sacrificed and adipose tissue samples were excised at necropsy. Extracts of fat and feces samples were analyzed by gas-liquid chromatography (GLC) on column packings of different polarity. Results of this study indicated that no significant biotransformation of lindane to HCB occurred in the female Fischer 344 rat.     

Comments on Comparison of hospitalization rates in patients with community-acquired pneumonia treated with 10 days of telithromycin or clarithromycin and Comparison of hospitalization rates in patients with community-acquired pneumonia treated with telithromycin for 5 or 7 days or clarithromycin or 10 days

ABSTRACT

Objective: Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered with extended interval dosing. Patient preferences were assessed for once-monthly versus once-weekly bisphosphonate treatment using a previously developed, open-label, cross-over trial design.

Research design and methods: This was a 6‐month, prospective, randomized, open-label, multi-center study with a two-period and two-sequence cross-over treatment design. After screening, eligible patients (postmenopausal women with osteoporosis) were randomized to once-monthly ibandronate 150?mg followed by once-weekly alendronate 70?mg for a total of 6 months (Sequence A) or once-weekly alendronate followed by once-monthly ibandronate for a total of 6 months (Sequence B). The primary objective was to evaluate patient-reported preference for either the once-monthly ibandronate regimen or the once-weekly alendronate regimen based on responses to a preference questionnaire.

Results: A total of 342 patients were enrolled into this study (Sequence A, 170; Sequence B, 172). In the primary analysis of patient preference, 71.4% of women selected once-monthly ibandronate and 28.6% of women selected once-weekly alendronate. Overall, 66.1% preferred the once-monthly ibandronate regimen to the once-weekly alendronate regimen (26.5%) and 7.4% of participants stated no preference for either regimen. The preference rate for once-monthly ibandronate was statistically significant (?p < 0.0001). ‘Ease of following a treatment regimen for a long time’ was the most common reason given for patient preference for both the once-monthly ibandronate (61%, 169/276) and once-weekly alendronate (25%, 70/276) regimens. Additionally, 17% (47/276) of patients who preferred once-monthly ibandronate chose ‘it is easier to tolerate side effects’ as did 4.3% (12/276) of patients who preferred alendronate. Significantly more women found once-monthly ibandronate to be more convenient (?p < 0.0001).

Conclusions: Significantly more women with postmenopausal osteoporosis preferred once-monthly ibandronate therapy to once-weekly alendronate therapy, and found the once-monthly regimen to be more convenient. Ease of following a treatment regimen for a long time was the most common reason given for the patients’ preferences.     

Monthly dosing with risedronate 50 mg on three consecutive days a month compared with daily dosing with risedronate 5 mg: a 6-month pilot study

ABSTRACT

Objective: Risedronate 5?mg daily significantly reduces the incidence of vertebral and non-vertebral osteoporotic fractures in postmenopausal women. We compared the efficacy and tolerability of risedronate 50?mg administered on 3 consecutive days per month, with and without a loading dose, with those of risedronate 5?mg daily in a randomized, double-blind study.

Methods: Subjects were postmenopausal women 65–80 years old with low bone mineral density (BMD) (T-score ≤ –2). Subjects received risedronate 5?mg daily for 6 months (n = 48), risedronate 150?mg (50-mg doses on 3 consecutive days) monthly for 6 months (n = 50), or a loading dose of risedronate 15?mg daily for 1 month followed by 150?mg (50-mg doses on 3 consecutive days) monthly for 5 months (n = 52).

Results: Within 1 week, statistically significant reductions in urine N-telopeptide, the primary efficacy measure, were observed in all three groups. After 6 months, the least squares (LS) mean differences (95% confidence intervals [CI]) from the change in the 5?mg daily group (–39.88) were –3.54% (–15.71; 8.64) for the 150?mg monthly and –2.02% (–14.13;10.10) for the loading dose + 150?mg monthly groups. Mean percent changes in serum alpha-C-telopeptide, bone-specific alkaline phosphatase, and BMD, secondary efficacy measures, after 6 months were also similar for the three groups. The LS mean differences (95% CI) from the mean percent change in BMD in the 5?mg daily group (3.22%) were 0.20 (–1.15; 1.55) for the 150?mg monthly and –0.58 (–1.93; 0.76) for the loading dose + 150?mg monthly groups. The safety profile of the monthly regimens was similar to that of the 5?mg daily regimen and consistent with product labeling.

Conclusions: A monthly regimen of risedronate 50?mg on 3 consecutive days per month was similar to risedronate 5?mg daily with respect to its effect in suppressing bone turnover and increasing BMD and its safety profile in women with postmenopausal osteoporosis. This study was not powered to be a confirmatory trial for non-inferiority; therefore, additional study is needed.     

Electrical stimulation prolongs the survival days of leukemic mice treated with methotrexate

To investigate effects of electrical stimulation on survival days of leukemic mice treated with methotrexate (MTX), L1210-bearing mice were treated by MTX and calcium folinate (leucovorin) rescue therapy (MTX: 400 mg/kg, followed by leucovorin at the dose of 7.5 mg/kg at 8, 15 and 24 hr after MTX) under electrical stimulation (foot shock: shock amplitude, 0.4 mA; voltage, 60-100 V/cm; shock duration, 5 sec; frequency, 0.5 Hz) of various lengths. The survival days were significantly prolonged by 6-hr electrical stimulation in combination with MTX, while plasma MTX concentrations and pharmacokinetic parameters such as the area under the curve (AUC-12 hr) and clearance (CL) were not significantly altered. Psychological stress did not alter the efficacy of MTX in the communication box paradigm. Amplified efficacy of MTX was shown in a length-dependent manner when electrical stimulation of various lengths were applied to L1210-bearing mice.