In the present study we found that after a single oral dose of 1,800 mg of praziquantel, following a high-lipid diet and a high-carbohydrate diet, the maximum levels in plasma increased 243 and 515% and the area under the plasma concentration curve from 0 to 8 h increased 180 and 271%, respectively.Nine healthy volunteers participated in the study. The mean age was 33.44 years (range, 26 to 47 years), and the mean weight was 72.22 Ϯ 11.29 kg. The protocol was approved by the local ethics committee, and informed written consent was obtained from each subject after detailed explanation of the purpose and risks of the study. Subjects did not take any other medication or alcohol for at least 15 days prior to the study.Volunteers were randomly separated into three groups of three subjects each. Group I received three tablets of 600 mg of praziquantel (1,800 mg) after 10 h of fasting; group II received the same dose of praziquantel immediately after administration of a high-fat diet, and group III received the same dose of praziquantel after a high-carbohydrate diet. Volunteers received a standard lunch 4 h after drug ingestion. The study was repeated in a crossover design allowing 1 week of washout between treatments. Blood samples were obtained through an indwelling catheter placed in the antecubital vein 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, and 8.0 h after the drug administration. Samples were centrifuged; the plasma was separated and stored at Ϫ4°C until analysis.The high-fat diet consisted of two fried eggs, one slice of ham, orange juice, and milk (200 ml) (protein, 19.63%; fat, 32.44%; and carbohydrate, 47.91%; 656 cal); the high-carbohydrate diet consisted of four tortillas, tomato, chicken (100 g), a slice of white bread, and a glass (200 ml) of orange juice (protein, 15.30%; fat, 10.54%, and carbohydrate, 74.15%; 674.5 cal).Praziquantel in plasma was determined using a high-performance liquid chromatography assay as previously reported (1). The method was linear from 15.6 to 8,000 ng/ml. The limit of quantitation was 15.6 ng/ml. The maximum within-day coefficient of variation was 7.9% at 15.6 ng/ml, and the mean value FIG. 1. Mean concentration in plasma (ϩstandard error of the mean) of praziquantel in healthy volunteers treated with a single oral dose of 1,800 mg (three tablets of 600 mg) during fasting (F) or immediately after a high-fat (‚) or a high-carbohydrate (s) breakfast.

Study about the relation between aspirin use and the risk of colorectal cancer (Sept. 7 issue), 1 a key question was whether the investigation inadvertently identified women who were resistant to colorectal cancer. A number of potentially confounding factors, including family history of colorectal cancer, smoking history, alcohol consumption, diet, and level of physical activity, were considered in the data analysis. Unaddressed was the effect of hormone-replacement therapy on the risk of colorectal cancer in the study population. Data from the Nurses' Health Study on hormone-replacement therapy and its relation to colorectal cancer have suggested a protective effect of this therapy against colon cancer. 2 Evidence linking hormone-replacement therapy and a reduced risk of colon cancer is also available from other studies. 3,4 Could the authors comment on whether women in their study who used aspirin two or more times a week were also more likely to be receiving hormone-replacement therapy?It was reported previously that the relation between the risk of colorectal cancer and the use of nonsteroidal antiinflammatory drugs (NSAIDs) -almost entirely aspirin -depended more on current use of NSAIDs than on previous use discontinued for at least a year. 5 It would be interesting to know more about this aspect of the data from the Nurses' Health Study. 1. Giovannucci E, Egan KM, Hunter DJ, et al. Aspirin and the risk of colorectal cancer in women. N Engl J Med 1995;333:609-14. 2. Chute CG, Willett WC, Colditz GA, Stampfer MJ, Rosner B, Speizer FE. A prospective study of reproductive history and exogenous estrogens on the risk of colorectal cancer in women. Epidemiology 1991;2:201-7. 3. Newcomb PA, Storer BE. Postmenopausal hormone use and risk of largebowel cancer. J Natl Cancer Inst 1995;87:1067-71. 4. Calle EE, Miracle-McMahill HL, Thun MJ, Heath CW Jr. Estrogen replacement therapy and risk of fatal colon cancer in a prospective cohort of postmenopausal women.Letters to the Editor are considered for publication (subject to editing and abridgment) provided they do not contain material that has been submitted or published elsewhere. Please note the following:• Your letter must be typewritten and triple-spaced. • Its text, not including references, must not exceed 400 words (please include a word count). • It must have no more than five references and one figure or table.• It should not be signed by more than three authors. • Letters referring to a recent Journal article must be received within four weeks of its publication. • Please include your full address, telephone number, and fax number (if you have one). Our fax numbers: 617-739-9864 and 617-734-4457Our Internet address: letters@edit.nejm.orgWe cannot acknowledge receipt of your letter, but we will notify you when we have made a decision about publication. We are unable to provide prepublication proofs. Please enclose a stamped, self-addressed envelope if you want unpublished material returned to you.Financial associations or other possible conflicts of interest mu...

A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weight given at 2-h intervals, alone and with the simultaneous administration of cimetidine. Each volunteer received both regimens in a randomized crossover design. Blood samples were taken during a period of 12 h, and praziquantel concentration was measured by high-performance liquid chromatography. Levels of praziquantel in plasma remained above 300 ng/ml during a period of 12 h; they increased 100% when cimetidine was jointly administered. Compared with other regimens, the high levels obtained and the longer duration of action seem to be advantageous in prolonging the exposure of the parasites to the drug and support previous clinical experience showing that the treatment of neurocysticercosis with praziquantel can be reduced from 2 weeks to 1 day with the drug still retaining its cysticidal properties. Moreover, simultaneous administration of praziquantel and cimetidine could improve further the efficacy of the single-day therapy for cysticercosis and other parasitic diseases, such as schistosomiasis.

After a single oral dose of praziquantel with 250 ml of grapefruit juice, the area under the concentration-time curve and the maximum concentration in plasma of praziquantel (C max ) were significantly increased (C max for water treatment, 637.71 ؎ 128.5 ng/ml; and C max for grapefruit juice treatment, 1,037.65 ؎ 305.7 ng/ml, P < 0.05). No statistically significant differences were found in the time to maximum concentration of drug in plasma or elimination half-life.Grapefruit juice increases the bioavailability of a variety of drugs (3,4,10,11,13,14,18), but it scarcely affects the elimination half-life (t 1/2 ). These findings suggest that grapefruit juice alters the first-pass metabolism mainly by suppression of the cytochrome P450 enzyme CYP3A4 in the small intestine (1,2,15).Praziquantel is an effective antihelmintic drug, widely used in the treatment of various parasitic diseases, including brain cysticercosis (7,20). It has been shown that the drug undergoes extensive metabolism by cytochrome P450; therefore, the systemic bioavailability of praziquantel is low and variable despite its almost complete gastrointestinal absorption (17). The specific cytochrome P450 enzymes involved in the metabolism of praziquantel in humans have not been characterized (5), but a significant inhibition of praziquantel hydroxylation by compounds that are inhibitors for 3A isoforms of cytochrome P450 has been observed in microsomes isolated from rat liver (16). In previous studies in humans, it was shown that cimetidine (an inhibitor of the microsomal cytochrome P450 mixed-function oxidase system) or simultaneous food administration increased the levels in plasma of praziquantel (6, 12); therefore, the aim of this study was to investigate the effect of the ingestion of grapefruit juice on the pharmacokinetics of praziquantel.Eighteen healthy male volunteers (age range, 23 to 37 years; mean, 28.8 Ϯ 5.4 years) participated in the study. Medical examination before the study showed that they were healthy and had normal results in laboratory tests that included complete blood count, serum chemistry measurement, hepatic test, and urinalysis. The volunteers signed an informed consent after detailed explanation about the purpose and design of the study, as well as the possible risks. The study was approved by the local ethics committee.The study was performed using a balanced randomized crossover design. Volunteers were separated in two groups of nine subjects each and received three tablets of 600 mg of praziquantel (Cisticid; Merck) with 250 ml of water or 250 ml of commercially squeezed grapefruit juice (Florida 7; lot L-2 05:51; Zano Alimentos S.A. de C.V., Mexico City, Mexico).The same lot number was used throughout the study. The interval between tests was 1 week. Blood samples were obtained through an indwelling catheter placed in the antecubital vein at 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, and 8.0 h after the drug administration. Samples were centrifuged; the plasma was separated and stored at Ϫ4°C until an...