Biomedical subjects

I Setnikar

Publications and source records attributed to I Setnikar.

At least 37 records · Page 2Linked to original sources

PubMed1998

Bioavailability and pharmacokinetic characteristics of two monofluorophosphate preparations with calcium supplement.

Two studies on the rate and extent of bioavailability of fluoride from a single dose of oral preparations of sodium monofluorophosphate (Na2FPO3) combined with calcium supplement were conducted according to a cross-over design on 18 (Study 1) and 20 (Study 2) male healthy volunteers, respectively. Evaluated were: a) tablets containing 76 mg Na2FPO3 (Ref1); b) chewable tablets containing 76 mg Na2FPO3 and 1250 mg calcium carbonate (Test 1); c) effervescent tablets containing 76 mg Na2FPO and 3240 mg calcium lactogluconate/carbonate (Ref 2); d) effervescent tablets containing 76 mg Na2FPO3 and 1250 mg calcium carbonate (Test 2). In all preparations Na2FPO3 was equivalent to 10 mg elemental F. The calcium supplement was equivalent to 500 mg elemental Ca. Fluoride was assayed in serum and in urine by a gas chromatographic method with a limit of quantitation of 10 ng/ml. Test 1 was found equivalent to Ref1 with regard to rate and extent of bioavailability of fluoride in serum. Test 2 (effervescent tablets resulting in an oral solution of Na2FPO3 and calcium salts) was found bioequivalent in rate and extent to Ref2 (effervescent tablets authorized for marketing with the same content in F and Ca equivalents as Test 2). The pharmacokinetics of fluoride from all investigated preparations was characterized by a short lag time, a rapid absorption, a Cmax of fluoride of 291-351 ng/ml (without significant differences between preparations) reached 30-75 min after administration, and a terminal t1/2 of 6-14 h. About 50% of the absorbed fluoride was eliminated with the urine (from 0 to infinity time). The kur.el was 0.06 h-1. The renal clearance 65 ml/min. The preparations were well tolerated by the subjects. In conclusion, Test1 and Test2 represent combinations of Na2FPO3 with calcium supplement which are well tolerated and provide a rapid, reliable and practically complete bioavailability of fluoride. They are therefore suitable for the bone-forming therapy of osteoporosis.

Adolescent↗

PubMed1997

Pharmacokinetics of estradiol and of estrone during application of three strengths of an estradiol transdermal patch with active matrix.

The pharmacokinetic pattern of estradiol (CAS 50-28-2) and of estrone (CAS 53-16-7) during and after application of three strengths of a new transdermal estradiol patch (Dermestril) with active matrix was investigated in a cross-over study in 24 women in natural or surgical menopause. Free estradiol and estrone were assayed by GC-MS on plasma samples obtained during a 4-day application on the upper buttocks of the patches with 3 strengths and release rates of 25, 50 and 100 micrograms/day estradiol. The estradiol concentrations in plasma increased from 0-10 pg/ml typical of menopause to average concentrations of 23, 40 and 79 pg/ml during the application of the new estradiol transdermal patches with the three strengths. The concentrations of estradiol are in the range of those during the early follicular phase in women in fertile age. The increases were linearly related with the strength of the patches. Upon removal of the patches the estradiol concentrations returned to the basal low values in 8-24 h. Retarded with regard to estradiol, there was also an increase of estrone, from basal average concentrations of 22-32 pg/ml up to 31, 39 and 60 pg/ml. The increase of estrone was less pronounced than that of estradiol. Also estrone returned to its basal concentrations 24 h after removal of the patches. The estradiol/ estrone ratio from very low values typical of postmenopause increased to values of about 1, i.e. in the range of those found during the fertile age of woman. The adhesion of the patches was satisfying, provided that direct rough frictions were avoided. The patches were locally well tolerated, with rare mild and transient irritating effects on the skin. Also the systemic tolerability was good, with occasional mild or moderate side effects typical of estradiol (headache, mastodynia and pelvic heaviness) which in the practical use can be easily avoided by the application of patches of lower strength.

Administration, Cutaneous↗

PubMed1996

Bioavailability of estradiol from two transdermal patches.

The bioavailability of estradiol (CAS 50-28-2; E2) from a new "matrix type" estradiol transdermal patch (Dermestril; Test patch) was compared to that of the widely used "liquid-reservoir, membrane-controlled type" transdermal patch (Reference patch) in a two-way randomized cross-over study on 28 healthy postmenopausal women, during a single 4-day application of 2 patches (total content 8 mg E2, total nominal release rate 100 micrograms E2 in 24 h). Evaluated from the AUC0-96h, the extent of bioavailability was practically the same for the two patch types. Conversely the rate of bioavailability was significantly different, because from the Reference patch the release rate is fast in the first 24 h, leading to an E2 peak at 8 h and to a Cmax in average at 23 h. But after the 2nd day the release/absorption rate declines markedly, leading to E2 serum concentrations at the 3rd and 4th days possibly below the effective threshold. From the Test patch the release/absorption rate of E2 is more constant, leading to sustained E2 concentrations during the 4 days of application, with smaller fluctuations than during application of the Reference patch. In conclusion the Test patch can be considered practically bioequivalent to the Reference patch with regard to the extent of absorption, but not with regard to the rate of absorption, because the E2 concentrations in serum are more constant during the application of the Test transdermal patch than during the application of the Reference.

Administration, Cutaneous↗

PubMed1996

Pharmacokinetics of estradiol and of estrone during repeated transdermal or oral administration of estradiol.

The estradiol (CAS 50-28-2, E2) and estrone (CAS 53-16-7, E1) concentrations in blood were investigated during a 3-week twice weekly application of an E2 transdermal patch, or daily oral administration of E2 tablets. The transdermal patch (Dermestril 50, hereinafter called "Patch") contains 4 mg E2 and delivers daily 50 micrograms E2. The E2 tablets (hereinafter called "Tablet") contains 2 mg micronized E2. The study was performed on 32 healthy postmenopausal women randomly assigned to two parallel groups, each of 16 subjects, one treated with Patch and the other with Tablet. During the first transdermal Patch application, E2 reached effective concentrations of 30 pg/ml of more 12 h after application. During the following 5 applications the concentrations of E2 remained rather constant (fluctuation = 0.65). The study state was reached with the second Patch, with an average concentration (Cav) of 35 pg/ml. After removal of the last Patch, the E2 concentrations returned to the basal levels within 12 h. The E1 concentrations reached the maximum concentration (Cmax) of 48 pg/ml 41 h after the first Patch application and then remained rather constant (fluctuation = 0.28), with a Cav at steady state of 47 pg/ml. During the oral administration of the first Tablet, E2 reached the peak of 1084 pg/ml 49 min after administration and then decreased rapidly in the following 3 h. There was a progressive cumulation of E2 until steady state, which was reached after the 5th Tablets with a Cav of 418 pg/ml i.e. 12.0 times greater than during Patch, and very large pulses of E2 (fluctuation = 3.68). The E1 concentrations reached the peak of 334 pg/ml 4.28 h after the first administration. The steady was reached with the 14th daily administration. There were Large pulses of E1 (fluctuation = 1.15). The Cav was 441 pg/ml, i.e. 9.4 times greater than during Patch. In conclusion the twice weekly application of the transdermal Patch elicits rather constant and therapeutically effective blood concentrations of E2 and E1. In contrast, the daily oral administration of E2 Tablets elicits large pulses of E2 and E1, and exposes the subjects to high concentrations of E2 and of E1, which are 12.0 and 9.4 times greater, respectively, than those elicited by the Patch. Both treatments were fairly well tolerated, and no withdrawal of the medications during the study was necessary.

Administration, Cutaneous↗

PubMed1994

Glucosamine sulfate in osteoarthritis of the knee.

Glucosamine sulfate is a drug used for the treatment of osteoarthritis (OA), based on its pharmacological and metabolic activities on the cartilage and chondrocytes, complemented by mild anti-inflammatory properties and a favorable pharmacokinetic profile. The aim of this study was to define the activity and safety of glucosamine sulfate on the symptoms of patients with OA, using a multicenter, randomized, placebo-controlled, double-blind, parallel-group study design. The study included 252 outpatients with OA of the knee (Lequesne's criteria), radiological stage between I and III, and Lequesne's severity index of at least 4 points and symptoms for at least 6 months. Patients were treated with either placebo or oral glucosamine sulfate 500 mg t.i.d. for 4 weeks, with weekly, with weekly clinic visits. Responders to treatment were defined as patients with a reduction of at least 3 points in the Lequesne's index with a positive overall assessment by the investigator. The Lequesne's index was 10.6 +/- 0.45 S.E.M. points in both groups at the start of the study. This decreased to 7.45 +/- 0.5 points in the treatment group (average 3.2) and 8.4 +/- 0.4 points in the placebo group (average 2.2) (P < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (N = 120) vs 38% with placebo (N = 121). These proportions were 52% vs 37% in an intention-to-treat analysis (P = 0.014 and 0.016, respectively; Fisher's Exact Test). The medications were well tolerated throughout the study, with no difference between the glucosamine and placebo treated groups. It is concluded that glucosamine sulfate may be a safe and effective symptomatic Slow Acting Drug for OA.

Administration, Oral↗

PubMed1994

Glucosamine sulfate compared to ibuprofen in osteoarthritis of the knee.

Glucosamine sulfate is able to stimulate proteoglycan synthesis by chondrocytes and has mild anti-inflammatory properties. In clinical trials, glucosamine sulfate was more effective than placebo in controlling the symptoms of osteoarthritis (OA). In order to better characterize this therapeutic activity, we conducted a randomized, double-blind, parallel-group study of glucosamine sulfate 500 mg t.i.d. vs ibuprofen 400 mg t.i.d., orally for 4 weeks. The study included 200 hospitalized patients with active OA of the knee, symptoms for at least 3 months and a Lequesne's index of at least 7 points. Patients were evaluated weekly. Response was defined as a reduction in the Lequesne's index by at least 2 points if the enrollment value was higher than 12 points, or by at least 1 point if the enrollment value was 12 or less points, together with a positive overall assessment by the investigator. The improvement tended to be sooner under ibuprofen (48% responders vs 28% after the 1st treatment week; P = 0.06, Fisher's Exact test), but there was no difference from the 2nd week onward, with a success rate of 52% in the ibuprofen group and of 48% in the glucosamine group (P = 0.67) at the end of treatment. The average Lequesne's index at enrollment was around 16 points and decreased by over 6 points in both groups, again with the above described trend. On the other hand, 35% of patients on ibuprofen reported adverse events, mainly of gastrointestinal origin, vs 6% adverse events with glucosamine (P < 0.001, Fisher's Exact test). The number of adverse event related drop-outs was different between the two groups (7% vs 1%, respectively; P = 0.035). Glucosamine sulfate was therefore as effective as ibuprofen on symptoms of knee OA. These data confirm glucosamine sulfate as a safe symptomatic Slow Acting Drug for OA.

Administration, Oral↗

PubMed1994

Efficacy and safety of intramuscular glucosamine sulfate in osteoarthritis of the knee. A randomised, placebo-controlled, double-blind study.

Glucosamine sulfate (Dona, CAS 29031-19-4) is a drug used in the treatment of osteoarthritis. When orally given, it is more effective than placebo and at least as effective as non-steroidal anti-inflammatory drugs in relieving osteoarthritis symptoms. The aim of this multicentre, randomised, placebo-controlled, double-blind, parallel-group study was to assess the efficacy and safety of glucosamine sulfate intramuscularly given on the same parameters. 155 out-patients with knee osteoarthritis (Lequesne's criteria), radiological stage between I and III, Lequesne's severity index of at least 4 points and symptoms for at least 6 months, were treated with i.m. glucosamine sulfate (or placebo) 400 mg twice a week for 6 weeks. Clinic visits were performed at enrollment, after a 2-week baseline, at weekly intervals during treatment and 2 weeks after drug discontinuation. Responders to treatment were considered those patients with a reduction of at least 3 points in the Lequesne index, together with a positive overall judgement by the investigator. The Lequesne index was slightly over 10 points in average in both groups at the beginning of treatment. A significant decrease in the index was observed for glucosamine compared to placebo (3.3 vs. 2.0 points in average, respectively; p < 0.05, Student's t-test). The responder rate in the evaluable patients was 55% with glucosamine (n = 73) and only 33% (n = 69) with placebo (p = 0.012, Fisher's Exact Test). According to the intention-to-treat approach, considering also drop-outs, these proportions were 51% vs. 30% (p = 0.015).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Pharmacokinetics of glucosamine in man.

The pharmacokinetics of glucosamine sulfate (CAS 29031-19-4) was investigated in 6 healthy male volunteers (2 per administration route) using 14C uniformly labelled glucosamine sulfate and administering it in single dose by intravenous (i.v.), intramuscular (i.m.) or oral route. The results show that after i.v. administration the radioactivity due to glucosamine appears in plasma and is rapidly eliminated, with an initial t1/2 of 0.28 h. 1-2 h after administration the radioactivity due to glucosamine disappears almost completely and is replaced by a radioactivity originating from plasma proteins, in which glucosamine or its metabolites are incorporated. This radioactivity reaches a peak after 8-10 h and then declines with a t1/2 of 70 h. About 28% of the administered radioactivity is recovered in the urine of the 120 h following the administration and less than 1% is recovered in the feces. After i.m. administration similar pharmacokinetic patterns are observed. After oral administration a proportion close to 90% of glucosamine sulfate is absorbed. Free glucosamine is not detectable in plasma. The radioactivity incorporated in the plasma proteins follows pharmacokinetic patterns which are similar to those after i.v. or i.m. administration, but its concentration in plasma is about 5 times smaller than that after parenteral administration. The AUC after oral administration is 26% of that after i.v., or i.m. administration. The smaller plasma levels of radioactivity after oral administration are probably due to a first pass effect in the liver which metabolizes a notable proportion of glucosamine into smaller molecules and ultimately to CO2, water and urea.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

Bioavailability and pharmacokinetics of fluoride from two glutamine monofluorophosphate preparations.

A two-way cross-over study was conducted on 12 Caucasian male healthy volunteers aged between 25 and 38 years in order to determine the bioavailability and pharmacokinetics of fluoride after single oral administration in fasting conditions of two products (tablets and powder for oral use) of L-glutamine monofluorophosphate (G-MFP, CAS 116420-36-1). The two products contained the equivalent of 10 mg F and the equivalent of 300 mg CA as calcium gluconate and calcium citrate. The two products were found bioequivalent with regard to the release of fluoride, both on the basis of the AUC and Cmax of fluoride in plasma and of the urinary excretion of fluoride during the 48 h following the administration. The pharmacokinetics of fluoride in plasma is characterized by a short lag time (< 6 min), a rapid absorption, a peak which is reached 0.5-1.0 h after administration, followed by a biphasic elimination. The first phase with a k alpha of 1.8 h-1 is followed by a slower phase with a K beta of 0.14 h-1. Probably the terminal elimination rate is slower, about 0.05 h-1. The urinary excretion of fluoride during the 48 h after administration accounted for 40-50% of the administered dose of fluoride. The results are consistent with those found in previous studies after administration in fasting conditions of sodium fluoride or sodium monofluorophosphate alone or in combination with calcium salts.

Adult↗

PubMed1993

Effects of meal on the pharmacokinetics of fluoride from oral monofluorophosphate.

A two-treatment cross-over study was conducted on 8 Caucasian male healthy volunteers aged between 26 and 32 years in order to determine the influence of a standard meal on the bioavailability and pharmacokinetics of fluoride after a single oral administration of tablets containing the equivalent of 10 mg fluoride as sodium monofluorophosphate (Na-MFP, CAS 10163-15-2) in a fixed combination with 300 mg Ca as calcium gluconate and calcium citrate. The meal provoked a significant delay of the appearance of fluoride in blood (from 4 to 11 min), a slowing of the absorption rate, a prolongation of tmax (from 34 to 146 min), a decrease of Cmax (from 369 to 122 ng/ml) and a prolongation of the Mean Residence Time (from 7.1 to 9.1 h). However, the amount of fluoride entering in the systemic circulation was not affected by the meal, as shown by the ANOVA on the AUC and on the cumulated urinary excretion of fluoride in the 48 h following the administration of Na-MFP. It is concluded that appropriate meals do not influence the amount of absorbed fluoride from Na-MFP, and that they modify the rate of absorption with pattern that may improve the safety and possibly also the efficacy of Na-MFP.

Administration, Oral↗

PubMed1992

Antireactive properties of "chondroprotective" drugs.

The medicinal therapy of osteoarthritis is based on the use of analgesics, NSAIDs and corticosteroids to relieve pain and inflammation. In addition, "chondroprotective" agents (CPA) are used to stop the evolution of the disease. In this review the biochemical and pharmacological activities of some of the most widely used CPAs are described. All of these show more or less marked antiinflammatory activities, which for some of them are the result of an inhibition of cyclo-oxygenase and of prostaglandin biosynthesis, in which case they should be more properly classified as mild NSAIDs. Only two of the CPAs reviewed, diacerein and D-glucosamine sulfate, elicit antiinflammatory and antireactive effects without significant inhibition of the prostaglandin biosynthesis. These agents have also remarkable chondroprotective effects, and only these two agents should be classified as true CPAs. In particular glucosamine sulfate, which naturally occurs in the human body and is almost devoid of toxicity, is suitable for long-term therapeutic use. This, with its chondrometabolic, antireactive and antiarthritic properties, represents the pharmacological rationale for the use of glucosamine sulfate as a disease-modifying agent in osteoarthritis.

Animals↗

PubMed1992

Sodium fluoride-induced gastric mucosal lesions: comparison with sodium monofluorophosphate.

In a randomized double-blind study with two parallel groups of 10 male healthy volunteers each the response of gastric mucosa after a 7 days ingestion of sodium fluoride tablets (NaF) or sodium monofluorophosphate tablets (MFP) was compared. Gastroscopic evaluations were performed before treatment, day 1 and day 7. Simultaneously blood samples were collected for determination of laboratory data and serum fluoride values. In the MFP-group no severe gastric lesions were observed, whereas in the NaF-group in 7 of the 10 subjects significant gastric mucosal lesions including acute hemorrhages and free blood in the gastric lumen were found. The differences of the lesions scores in both groups were statistically significant (p = 0.0015). The serum fluoride content was comparable in both treatment groups. Possible adverse drug reactions were reported in 4 subjects with NaF and in 1 subject with MFP. In summary, under the experimental conditions used MFP is well tolerated by the stomach while NaF produces significant gastric mucosal lesions.

Adult↗

PubMed1991

Antireactive properties of glucosamine sulfate.

Glucosamine (CAS 3416-24-8) is an aminomonosaccharide naturally occurring in the human body. It was tested for antiinflammatory activities and it showed to protect against the edema provoked in the rat paw by carrageenin, dextran, formalin, but not against the edema provoked by specific inflammation mediators, such as bradykinin, serotonin, histamine. Glucosamine protected against pleurities provoked in the rat by carrageenin, but not against that provoked by bradykinin. Furthermore glucosamine protected against peritonitis provoked in the rat by formalin and in the mouse by acetic acid. Glucosamine did not show antinoceptive properties against writings provoked by i.p. phenylquinone in the mouse. Glucosamine did not show inhibiting activities on cyclooxygenase or on the proteolytic enzymes in the inflamed paw of the rat, but it was able to inhibit in vitro superoxide generation and lysosomial enzymes of the liver. The potency of glucosamine on the antiinflammatory tests was lower than that of acetylsalicylic acid and much lower than that of indomethacin. Its acute toxicity, however, and notably the toxicity on the gastrointestinal tract is very low, practically absent. The pharmacological therapeutic index of glucosamine with regard to the antiinflammatory activities seems therefore comparable or superior to that of the known non-steroidal anti-inflammatories.

Analgesics↗

PubMed1991

Antiarthritic effects of glucosamine sulfate studied in animal models.

The antireactive activity of glucosamine sulfate (GS) (CAS 29031-19-4) was tested in the rat in experimental models of subacute inflammation (sponge granuloma and croton oil granuloma), on subacute mechanical arthritis (kaolin arthritis) and in immunological-reactive arthritis and generalized inflammation (adjuvant arthritis). On these models GS was found effective in oral daily doses of 50-800 mg/kg. Tne potency of GS in comparison of that of indometacin used in the same tests as reference substance was found 50-300 times lower. Since, however, the toxicity of indometacin in chronic toxicity experiments is 1000-4000 times larger, the therapeutic margin with regard to prolonged treatments of inflammatory disorders results 10-30 times more favourable for GS than for indometacin. GS can therefore be considered as a drug of choice for prolonged oral treatment of rheumatic disorders.

Animals↗

PubMed1990

Effect of loxiglumide on gallbladder contractile response to cerulein and food in humans.

The present study investigated the effect of loxiglumide, a new selective cholecystokinin-receptor antagonist, on the gallbladder contractile responses to caerulein and to food in humans. In 6 healthy men, the gallbladder emptying driven by intravenous infusion of stepwise increasing doses of cerulein (10-80 ng/kg . h) and that induced by a 550-cal standard meal were monitored by ultrasonography. In both sets of experiments, the effect of loxiglumide was tested at various infusional rates against a control infusion of saline. An infusional rate of 2.5 mg/kg . h of loxiglumide abolished the gallbladder response even to maximal doses of cerulein, whereas a rate of 1.0 mg/kg . h counteracted the cholecystokinetic activity of cerulein up to the dose of 20 ng/kg . h. In postprandial experiments, the cholecystokinin antagonist dose-dependently inhibited the physiologic gallbladder contraction. The maximal gallbladder emptying, which always occurred 85 min after the meal, was 71.1% +/- 3.3% of basal volume in control studies, 39.2% +/- 1.8% during infusion of 2.5 mg/kg . h of loxiglumide, and 17.3% +/- 5.9% when 5.0 mg/kg . h were infused. A dose of 7.5 mg/kg . h of loxiglumide was able to prevent any postprandial emptying of the gallbladder. The present study shows that a selective cholecystokinin receptorial blockade competitively antagonizes cerulein-induced gallbladder contraction and dose-dependently inhibits postprandial gallbladder emptying.

Adult↗

PubMed1990

Effects of a cholecystokinin receptor antagonist on intestinal phase of pancreatic and biliary responses in man.

The present study was designed (a) to characterize the activity of loxiglumide as a peripheral cholecystokinin (CCK) antagonist in healthy human subjects, and (b) to determine whether CCK is a physiologic regulator of the intestinal phase of meal-stimulated exocrine pancreatic and biliary secretions in man. Intravenous loxiglumide (22 mumol/kg per h) was highly potent in antagonizing CCK8-induced pancreatic enzyme and bile acid secretion as well as pancreatic polypeptide release. The potency and selectivity of loxiglumide as an antagonist of CCK provides the tool for evaluating the role of CCK as a physiological mediator of meal-induced pancreatic and biliary responses in humans. Infusion of a liquid test meal into the duodenum evoked an immediate response of pancreatic enzyme and bilirubin outputs, respectively. Intravenous loxiglumide significantly inhibited the meal-induced pancreatic amylase output by 63% (P less than 0.05), lipase output by 43% (P less than 0.05), and bilirubin output by 59% (P less than 0.05). These data suggest that CCK is a physiological mediator of the intestinal phase of meal-stimulated pancreatic and biliary responses.

Adult↗

PubMed1990

Bioequivalence of sodium monofluorophosphate with sodium fluoride and compatibility with calcium.

The study was conducted in a triple cross-over on 12 healthy Caucasian volunteers (4 males and 8 females) of an age between 23 and 44 years. The following products were given in a single oral dose in fasting state. 1. Solution of 29.18 mg of sodium fluoride in 80 ml of water (reference NaF solution). 2. Solution of 100 mg sodium monofluorophosphate (CAS 10163-15-2) in 80 ml of water (Na2FPO3 solution). 3. Tablets with 100 mg sodium monofluorophosphate and 1250 mg calcium carbonate (Na2FPO3 + Ca tablets). The three products were equivalent in fluorine content (13.2 mg). The bioavailability of fluorine was evaluated on the basis of the plasma levels and of the urinary excretion of fluoride. After administration of the products, fluoride appeared in blood with a lag time smaller than 0.05 h and invaded the blood with a t1/2 from 0.07 to 0.12 h. The Cmax of fluoride in plasma was 412-466 ng/ml at a tmax of 0.5-0.7 h. The AUCs of fluoride after Na2FPO3 solution and after Na2FPO3 tablets were within the 0.80-1.20 bioequivalence limits with regard to the AUC after NaF solution. The three products can therefore be considered bioequivalent according to the Westlake criteria. In the 24 h following the administration, the urinary excretion of fluoride accounted for 51 +/- 10%, 46 +/- 6% and 47 +/- 8% of the administered dose, respectively for NaF solution, Na2FPO3 solution and Na2FPO3 + Ca tablets. The difference between the three products was statistically not significant and confirms their bioequivalence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Relative bioavailability of fluoride from monofluorophosphate tablets after single oral administration.

The study was conducted on 12 healthy male Caucasian volunteers of an average age of 27.8 +/- 4.0 years with single oral doses of the following products: 1. sodium monofluorophosphate tablets (MFP-tablets, Mono-Tridin); 2. aqueous solution of 23.2 mg of sodium fluoride (NaF solution-reference); 3. aqueous solution of sodium monofluorophosphate (MFP solution). The three products were equivalent in fluorine content with 10.5 mg F. The bioavailability was evaluated on the basis of the plasma levels and of the urinary excretion of fluoride. The study was designed as a triple latin-square crossover and each subject received the three products in three different periods, at empty stomach. After administration of the products, fluoride appeared quickly in blood (lag time between 0.07 and 0.13 h) and invaded rapidly the blood (invasion t1/2 from 0.04 to 0.15 h). The Cmax of fluoride in plasma was 439 ng/ml at tmax of 1.08 h after MFP tablets, 430 ng/ml at a tmax of 0.51 h after NaF solution and 403 ng/ml at tmax of 0.62 h after MFP solution. The differences for the Cmax were not statistically significant. The relative bioavailability of fluoride from MFP tablets, estimated from the AUC, was 1.35, and significantly larger than that from the reference NaF solution. Fluoride was eliminated from plasma with an initial fast rate (t1/2 from 0.68 to 1.03 h) and a terminal slower rate (t1/2 from 4.71 to 7.37 h). The plasma levels of fluoride were consistent with a two-compartment open pharmacokinetic model after extravascular administration. In the 24 h following the administration the urinary excretion of fluoride accounted for 50-53% of the administered dose, without significant difference between the three products. The three products were well tolerated and no systemic or gastric adverse reaction was recorded.

Adult↗