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Biomedical subjects

M Chaplin

Publications and source records attributed to M Chaplin.

14 recordsLinked to original sources
PubMed1989

Metabolic fate of the new anti-ulcer drug enprostil in animals. 1st communication: absorption, distribution and excretion in the mouse, rat and rabbit.

Absorption, distribution and excretion of [3H]-enprostil ((+-)-11a,15a-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorpr osta -4,5,13(t)-trienoic acid methyl ester, TA-84135), a new anti-ulcer prostaglandin, were studied in mice, rats and rabbits. Radioactivity associated with enprostil was rapidly absorbed from the gastrointestinal tract with Tmax values of 15 or 30 min. Absorption was also efficient inasmuch as approximately 80% of an oral dose was recovered in bile and urine in 24 h in bile duct-cannulated rats. Experiments in pylorus-ligated, bile duct-cannulated rats demonstrated that enprostil was mainly absorbed from the intestine, rather than from the stomach. In mice given oral doses of 2, 8 and 32 micrograms/kg, Cmax and AUC values of enprostil radioequivalents increased proportionately to the increase in dose, indicating linear kinetics over this dose range. Distribution of enprostil-associated radioactivity was investigated in rats by quantitating tritium in various tissues after the oral administration of [3H]-enprostil. Radioactivity in tissues was highest at 15 or 30 min after dosing. Highest levels of radioactivity were found in the stomach and intestines, the organs which came into direct contact with the dose, and the liver and kidney, the organs involved in excretion of enprostil. The rate of elimination of enprostil-associated radioactivity from all tissues and from plasma was similar. Enprostil-associated radioactivity did not accumulate in any tissue. Radioactivity was found in fetuses following oral administration of [3H]-enprostil to rats on the 12th or 19th day of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Metabolic fate of the new anti-ulcer drug enprostil in animals. 2nd communication: whole-body autoradiographic distribution of [3H]-enprostil in rats.

The distribution of radioactivity was studied by whole-body autoradiography in rats after oral or intravenous administration of [3H]-enprostil ((+/-)-11a-15a-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorp r osta-4,5,13(t)- trienoic acid methyl ester, TA-84135) at a dose of 23 micrograms/kg. After oral administration to male rats, radioactivity in almost all the tissues and organs reached a peak within 15 min to 1 h. The highest levels of radioactivity were found in the contents of the stomach and intestine. High levels of radioactivity were also observed in the liver and kidney, and moderate levels were found in the lung, blood, dental pulp and the walls of the stomach. Radioactivity was the lowest in the skeletal muscle, testis, eye and brain. After reaching peak levels, radioactivity in the body decreased gradually, and it was detected only in the excretory organs at 24 h after drug administration. The distribution pattern after the intravenous dose was essentially similar to that after oral administration. The distribution profile of radioactivity in non-pregnant female rats after an oral dose was similar to that in male rats. Placental transfer and excretion in milk of radioactivity was slight. When the affinity of this compound to the melanin-containing tissues such as the uveal tract of the eye and the hair follicle was examined using pigmented rats, no tendency to retention of radioactivity in these tissues was observed.

Administration, Oral↗
PubMed1989

Metabolic fate of the new anti-ulcer drug enprostil in animals. 3rd communication: tissue accumulation after consecutive oral administration of [3H]-enprostil in rats.

Accumulation characteristics of radioactivity in organs and tissues were investigated after oral administration of [3H]-enprostil ((+/-)-11a,15a-dihydroxy-9-oxo-16-phenoxy-17,18,19,20-tetranorp r osta-4,5,13(t)- trienoic acid methyl ester, TA-84135) to male rats once a day (20 micrograms/kg/d) for 1, 7 or 14 days. [3H]-Enprostil was found to be partially metabolized in vivo to volatile tritium (3H2O). The ratios of volatile tritium to total radioactivity in plasma increased with repeated administration of [3H]-enprostil and the levels of volatile tritium were almost equilibrated within 7 days of drug administration. The formation rate of volatile tritium was estimated to be 1-2% of the single dose. The blood levels of non-volatile radioactivity at 1 h after each daily dosing were nearly constant. The levels at 24 h, however, increased with repeated dosing. The levels of non-volatile radioactivity in most tissues at 1 h after the multiple administration (7 and 14 times) were higher than those after the single dose. At 24 h, levels were noticeable after multiple dosing even in the tissues in which levels below the detection limit were found after the single dose. From the comparison of the multiple-dose groups, the levels in most tissues attained steady state within 7 times dosing. The daily excretions of radioactivity in the urine, feces and expired air were constant throughout the period of consecutive administration. The total recovery of administered dose was 92%, which was similar to that achieved in the single-dosing group. As described above, the retention of non-volatile radioactivity was observed in most tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1985

A comparison of intranasal and oral flunisolide in the therapy of allergic rhinitis. Evidence for a topical effect.

Intranasal flunisolide is an effective treatment for allergic rhinitis. Flunisolide has high bioavailability when administered to normal subjects (50% of an intranasal dose reaches the systemic circulation) with minimal systemic effects. Bioavailability in patients with active rhinitis averages 62.4 +/- 15.7%. The oral dose bioequivalent to 100 micrograms intranasally is 500 micrograms. To define the comparative trial and systemic effects of intranasal flunisolide in patients with active allergic rhinitis, a multicenter, randomized, double-blind, placebo-controlled study was conducted during the 1983 ragweed hayfever season. Ninety-nine patients with ragweed hayfever for greater than or equal to 2 years and positive prick skin tests to ragweed were randomly allocated to one of three treatment groups: 0 = oral flunisolide 500 micrograms b.i.d. and intranasal placebo b.i.d.; N = intranasal flunisolide 50 micrograms per nostril b.i.d. and oral placebo b.i.d.; P = intranasal and oral placebo b.i.d. Treatment continued for 4 weeks. Patients kept daily symptom scores. Patients were evaluated by a blinded observer every 2 weeks and were globally evaluated at the study's end. Data were analyzed for each center and pooled. There were no significant differences in symptom severity of sneezing, nasal congestion, and throat itch in the 0 (oral flunisolide) and P (placebo) groups. N (nasal flunisolide) was significantly more effective than O or P (P less than or equal to 0.005) for each symptom for at least one 2-week period. Global evaluation demonstrated control of overall hayfever severity for N (nasal flunisolide) but not for O (oral flunisolide). We conclude that the therapeutic efficacy of flunisolide is achieved by topical and not by systemic action.

Administration, Intranasal↗