Nonheme-iron absorption, fecal ferritin excretion, and blood indexes of iron status in women consuming controlled lactoovovegetarian diets for 8 wk.
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BACKGROUND: The characteristics of vegetarian diets suggest that these diets would have lower dietary iron bioavailability than nonvegetarian diets, but there is no evidence of iron deficiency in vegetarians. OBJECTIVE: We evaluated the responsiveness of serum and fecal ferritin to differences in iron absorption from controlled lactoovovegetarian and nonvegetarian diets. DESIGN: Twenty-one women aged 20-42 y with serum ferritin concentrations from 6 to 149 microg/L consumed lactoovovegetarian and nonvegetarian weighed diets for 8 wk each (crossover design). The diets differed substantially in meat and phytic acid contents. Nonheme-iron absorption was measured from the whole diets after 4 wk by using extrinsic 59Fe and whole-body counting. Ferritin in extracts of fecal composites and in serum was measured by enzyme-linked immunosorbent assay the last 2 wk of each diet. RESULTS: Nonheme-iron absorption was less from the lactoovovegetarian diet than from the nonvegetarian diet (1.1% compared with 3.8%; P < 0.01; n = 10). Diet did not affect hemoglobin, transferrin saturation, erythrocyte protoporphyrin, or serum ferritin. Substantially less fecal ferritin was excreted with the lactoovovegetarian diet than with the nonvegetarian diet (1.1 compared with 6.0 microg/d, respectively; P < 0.01; n = 21). CONCLUSIONS: This research indicates 1) 70% lower nonheme-iron absorption from a lactoovovegetarian diet than from a nonvegetarian diet; 2) an associated decrease in fecal ferritin excretion, suggesting partial physiologic adaptation to increase the efficiency of iron absorption; and 3) an insensitivity of blood iron indexes, including serum ferritin, to substantial differences in dietary iron absorption for 8 wk. (+info)
Pharmacokinetics of aminolevulinic acid after oral and intravenous administration in dogs.
(26/3985)
The purpose of these studies was to examine the pharmacokinetics, oral bioavailability, and systemic side effects of aminolevulinic acid (ALA) in beagle dogs after oral and i.v. administration. Oral and i.v. doses of ALA (128 mg of ALA hydrochloride, equivalent to 100 mg of ALA) were administered to four animals using a crossover design. Animals were allowed a 2-week washout period between doses. Plasma ALA concentrations were determined using precolumn fluorescent derivatization and reversed-phase HPLC. Plasma concentrations after i.v. administration declined rapidly with a terminal half-life of 19.5 +/-2.5 min (mean +/- S.D.). Total body clearance and volume of distribution at steady state averaged 6.79+/-1.77 ml/min/kg and 259+/- 128 ml/kg, respectively. Peak plasma concentrations of ALA after oral administration ranged from 1.27 to 9.42 microgram/ml. Oral bioavailability in these animals averaged 41.2+/-14.8% (range, 23.5-58.5%). These studies demonstrate that oral administration may provide a convenient and efficient route of delivery of ALA for photodynamic therapy in patients. (+info)
Pharmacokinetics and bioavailability of oral 5'-deoxy-5-fluorouridine in cancer patients.
(27/3985)
AIMS: Oral administration of 5-fluorouracil (FUra), an important cytotoxic agent, is limited by a wide variation in bioavailability. 5'-deoxy-5-fluorouridine (dFUrd), a masked form of FUra, has shown promise clinically when given intravenously or orally as a solution or tablet. This study investigates the efficacy of an oral capsule formulation of dFUrd in generating continuous systemic levels of this compound in cancer patients. METHODS: Six patients with advanced intestinal or ovarian malignancies were given three cycles of dFUrd, days 1-5, at intervals of 4 weeks. The doses of dFUrd were 600 mg m-2 three times daily, 800 mg m-2 three times daily, and 1000 mg m-2 three times daily, on cycles one, two and three, respectively (total dose 36 g m-2 ). The initial dose in each cycle was given as a slow intravenous injection over 10 min, and the remainder orally. Plasma and urine levels of dFUrd and two of its metabolites, FUra and 5,6-dihydro-5-fluorouracil (FUraH2 ), were monitored in six patients at each dose level. RESULTS: All six patients completed the study, receiving three different doses over a 3 month period, following which one had achieved a partial response, one had stable disease, and four had developed progressive disease. Side-effects were negligible, and only two instances of transient diarrhoea WHO grade 1 were seen. Total body clearance (CLtot) of intravenous dFUrd decreased with increasing dose; 2.7, 2.0 and 1.3 l min-1 m-2, following doses of 600, 800 and 1000 mg m-2, respectively. The mean elimination half-life of intravenous dFUrd increased with the dose from 15 to 22 min. Oral dFUrd was rapidly absorbed with a lag time of less than 20 min. The mean elimination half-life (t1/2, z ) of oral dFUrd was 32-45 min in the dose range 600-1000 mg m-2. The AUC of FUra and FUraH2 increased overproportionally with increasing intravenous doses of dFUrd. The mean systemic bioavailability of oral dFUrd was 34-47%. CONCLUSIONS: dFUrd, which selectively releases the antimetabolite FUra in tumour cells, can be given orally at doses of 600-1000 mg m-2 three times daily for 5 days. The systemic levels achieved are equivalent to those seen following continuous infusions of dFUrd or FUra. Toxicity is tolerable, and further clinical investigation of oral dFUrd is warranted. (+info)
Chronopharmacology of intravenous and oral modified release verapamil.
(28/3985)
AIMS: Using a stable isotope technique which allows simultaneous and differential measuring of orally and intravenously administered drugs we compared the pharmacokinetics and pharmacodynamics of unlabelled modified release verapamil p.o. (steady state) and deuterated verapamil i.v. (single dose) following morning and evening administration. METHODS: Twelve female and 12 male healthy volunteers were studied in a randomized, crossover design. During the last day of each treatment period (day 6 and day 10) pharmacokinetics and pharmacodynamics (PR interval) of verapamil were assessed; 1 h before ingestion of a new R/S-verapamil 240 mg modified release formulation (08.00 h vs 20.00 h) a single dose of 10 mg d7-R/S-verapamil was administered intravenously. Serum levels of unlabelled and labelled R/S-verapamil were measured by gas chromatography/mass spectrometry. In selected samples of serum which were chosen at tmin,po and tmax,po the enantiomers were separated by chiral high-performance liquid chromatography in order to calculate R- to S-verapamil serum concentration ratios. RESULTS: We observed no significant differences in pharmacokinetics (AUCpo, Cmax, tmax, CLo, F and R/S enantiomer ratio) between morning and evening treatment with modified release verapamil and there was no influence of time of dosing on mean prolongation of PR interval. AUCiv, CL, Vss and d7-R/d7-S enantiomer ratio following verapamil i.v. did not show circadian variation. t1/2 was slightly but statistically significantly increased after the morning infusion. PR-prolongation was significantly greater after verapamil i.v. in the morning than in the evening. The 90% confidence intervals of the differences between morning and evening administration in AUCpo, Cmax and AUCiv were within the equivalence range of 0.8-1.25. CONCLUSIONS: Time of dosing has no significant influence on pharmacokinetics and pharmacodynamics of this new modified release formulation of verapamil. Circadian variation in presystemic metabolism of verapamil was not observed. (+info)
The relationship between pH and concentrations of antioxidants and vasoconstrictors in local anesthetic solutions.
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pH affects the efficacy of local anesthetics by determining the percentage of the lipid-soluble base form of the anesthetic available for diffusion and penetration of the nerve sheath. The purpose of this study was to determine the relationship between pH and the concentrations of antioxidant and vasoconstrictor in dental local anesthetic solutions over real-time and after accelerated aging. Several batches of lidocaine and mepivacaine with vasoconstrictors were tested. Results showed that, immediately upon receipt from the manufacturers, three batches were below the USP pH limit (pH 3.3), and two batches contained less than the minimum limit of vasoconstrictors (90%). Real-time tests on batches that were within normal limits revealed that solutions were stable past 4 yr. Accelerated aging tests revealed a strong correlation between a decrease in pH and loss of antioxidants and vasoconstrictors. In conclusion, a quality batch of local anesthetic should remain efficacious long past the manufacturer's stated shelf life; a batch that is less than optimal, or one that is exposed to environmental stresses, will degrade rapidly, and efficacy may be affected by decreases in pH and loss of vasoconstrictor. pH may be an inexpensive, readily available screening test for efficacy of local anesthetics. (+info)
Systemic availability and pharmacokinetics of nebulised budesonide in preschool children.
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AIM: To evaluate the systemic availability and basic pharmacokinetic parameters of budesonide after nebulisation and intravenous administration in preschool children with chronic asthma. METHODS: Plasma concentrations of budesonide were measured for three hours after an intravenous infusion of 125 micrograms budesonide. The children then inhaled a nominal dose of 1 mg budesonide through the mouthpiece of a Pari LC Jet Plus nebuliser connected to a Pari Master compressor, and the plasma concentrations of budesonide were measured for another six hours. The amount of budesonide inhaled by the patient ("dose to subject") was determined by subtracting from the amount of budesonide put into the nebuliser, the amount remaining in the nebuliser after nebulisation, the amount emitted to the ambient air (filter), and the amount found in the mouth rinsing water. RESULTS: Ten patients aged 3 to 6 years completed both the intravenous and the inhaled treatment. The mean dose to subject was 23% of the nominal dose. The systemic availability of budesonide was estimated to be 6.1% of the nominal dose (95% confidence intervals (CI), 4.6% to 8.1%) or 26.3% of the dose to subject (95% CI, 20.3% to 34.1%). Budesonide clearance was 0.54 l/min (95% CI, 0.46 to 0.62), steady state volume of distribution 55 litres (95% CI, 45 to 68), and the terminal half life was 2.3 hours (95% CI, 2.0 to 2.6). CONCLUSIONS: Approximately 6% of the nominal dose (26% of the dose to subject) reached the systemic circulation of young children after inhalation of nebulised budesonide. This is about half the systemic availability found in healthy adults using the same nebuliser. (+info)
The TNF-alpha system in heart failure and after heart transplantation: plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity.
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BACKGROUND: The two soluble tumour necrosis factor (TNF) receptors (sTNF-R1, sTNF-R2) can bind TNF-alpha, which is a cytokine with cardiodepressant properties. In heart failure and after heart transplantation, the TNF-alpha system is unbalanced, due to elevated levels of sTNF receptors. AIM: To assess the activity of the TNF-alpha system in patients with heart failure and after heart transplantation. METHODS: We measured TNF-alpha mRNA expression of peripheral blood mononuclear cells, plasma levels of TNF-alpha and sTNF reverse transcriptase receptors, using polymerase chain reaction and ELISA and performed a TNF-alpha binding capacity analysis, quantitating the buffer capacity of patients' plasma. RESULTS: In 11 patients with heart failure and in 15 cardiac allograft recipients, the TNF-alpha mRNA expression was comparable to controls. This level of mRNA was not accompanied by detectable TNF-alpha plasma levels. Significantly higher sTNF receptors levels were found in patients: ( P <0.001; ANOVA). The TNF-alpha binding capacity of patients' plasma was significantly increased, which led to decreased TNF-alpha recovery ( P<0.05). Both sTNF receptors showed a linear correlation with serum creatinine (sTNF-RI: r=0.92; sTNF-R2: r=0.82, P<0.001). CONCLUSIONS: The TNF-alpha mRNA expression and plasma levels show that the 'peripheral' TNF-alpha system is not activated. The high sTNF-receptors levels and their elevated TNF-alpha binding capacity, resulting in decreased TNF-alpha bioavailability, may contribute to an immunosuppressed state in these patients. (+info)
Pharmacokinetic study of single doses of oral fludarabine phosphate in patients with "low-grade" non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia.
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PURPOSE: Fludarabine phosphate (F-AMP), a purine analog, requires daily intravenous administration. A pharmacokinetic study of an oral formulation (10 mg immediate-release tablet) was undertaken in patients with "low-grade" non-Hodgkin's lymphoma and B-cell chronic lymphocytic leukemia. PATIENTS AND METHODS: Oral F-AMP was incorporated into the "conventional" treatment schedule. Single oral trial doses of 50, 70, and 90 mg of F-AMP were given on the first day of three cycles of treatment; a comparative 50-mg intravenous trial dose was given on the first day of the fourth cycle. Intravenous F-AMP (25 mg/m2) was given on days 2 to 5 at 4-week intervals. Pharmacokinetic samples taken after each trial dose were analyzed for plasma 2-fluoro-arabinofuranosyladenine (2F-ara-A) concentration (its main metabolite); area under the curve 0 to 24 hours (AUC(0-24h)) and maximum concentration (Cmax) were calculated. Eighteen patients received all three oral trial doses, and bioavailability was determined in 15 patients who completed four courses of therapy. RESULTS: Oral administration of F-AMP resulted in a dose-dependent increase in Cmax and AUC(0-24h) of 2F-ara-A and achieved an AUC(0-24h) similar to intravenous administration, although at a lower Cm. The linear increase in mean AUC(0-24h) by factors of 1.36 +/- 0.22 (mean +/- SD) and 1.72 +/- 0.31 corresponded well with the increase in oral dose from 50 to 70 mg (factor of 1.4) and 90 mg (factor of 1.8), respectively. Bioavailability (approximately 55%, with low intraindividual variation) and time to Cmax were dose independent. CONCLUSION: Oral doses of F-AMP can achieve an AUC(0-24h) of 2F-ara-A similar to intravenous administration, with dose-independent bioavailability. The tablet will greatly enhance the use of F-AMP in a palliative setting. (+info)