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Biomedical subjects

F Y Aoki

Publications and source records attributed to F Y Aoki.

At least 73 records · Page 4Linked to original sources
PubMed1985

Prophylactic amantadine dose and plasma concentration-effect relationships in healthy adults.

Amantadine dose, plasma concentration, prophylactic and adverse effect relationships for prevention of influenza A virus infection in healthy young adult subjects were investigated in a double-blind, placebo-controlled study. Seventy-four subjects with hemagglutination inhibition antibody titers less than or equal to 16 against an attenuated influenza A virus AF9/Montreal/3/72 (H3N2) were randomly allocated to groups taking 0 (placebo), 25, 100, or 150 mg amantadine syrup prophylactically twice a day for 31 doses. Eighteen other subjects were randomly allocated to control groups for investigation of drug toxicity (150 mg) or concurrent other virus infection (placebo). Steady-state trough plasma concentrations were 110 +/- 39, 302 +/- 80, and 572 +/- 207 ng/ml (X +/- SD) for the three amantadine doses and increased out of proportion to dose. Prophylaxis groups were challenged intranasally with virus after the fifth dose at steady state; control subjects received saline solution. No subject became ill. Input virus was recovered 48 or 72 hr after challenge from nose or throat swabs of nine of 21 subjects taking placebo, one of 18 subjects taking 100 mg amantadine, three of 18 subjects taking 25 mg amantadine, and six of 17 subjects taking 150 mg amantadine. There were no differences in seroconversion rates or adverse symptoms. Our data do not support a change in the recommended amantadine prophylactic dose for influenza A virus infection in healthy young adults. We defined trough steady-state plasma concentrations associated with the recommended amantadine dose of 100 mg twice a day that should be mimicked in devising dose schedules for populations with differing amantadine kinetics.

Adolescent↗
PubMed1985

Amantadine kinetics in healthy elderly men: implications for influenza prevention.

Amantadine kinetics were investigated in 10 healthy elderly men 60 to 76 yr old. We calculated a dose that would yield the same trough steady-state plasma amantadine concentration (Cpss; 300 ng/ml) as a 200 mg/day dose taken by young healthy adults; this dose prevents influenza A virus infection and is well tolerated by this population. With a one-compartment open model, kinetic parameters were calculated after a single dose of 25, 50, or 75 mg or the same dose twice a day for 10.5 days. Peak concentration occurred 4.0 to 8.0 hr after dosing, but the calculated AUC was proportional to dose, indicating that relative bioavailability was independent of dose. This was supported by recovery of 88% of the single doses in urine. No change in apparent volume of distribution was found. Log trough Cpss increased with dose. Trough Cpss varied less than 300% for equivalent doses. There was first-order elimination of drug from plasma, with a median t1/2 of 28.9 hr (range 18.5 to 45.0 hr), and elimination was independent of dose and creatinine clearance. The median ratio of renal amantadine clearance to creatinine clearance was 2.07 (range 0.64 to 4.20), suggesting renal tubular secretion. Compared to data from healthy young adults, the t1/2 was doubled and renal drug clearance was diminished in elderly men. To achieve the target trough Cpss of 300 ng/ml, healthy older men must take amantadine at a dose of 1.4 mg/kg/day, and we suggest that this is a rational dose for evaluation of efficacy and safety for influenza A prophylaxis in this population.

Age Factors↗
PubMed1985

Antiherpes effects and pharmacokinetic properties of 9-(4-hydroxybutyl) guanine and the (R) and (S) enantiomers of 9-(3,4-dihydroxybutyl)guanine.

Three acyclic guanosine analogs with similar structures, the (R) and (S) forms of 9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine, were compared for antiherpes activity in vivo and in vitro. The three guanosine analogs were viral thymidine kinase-dependent inhibitors of virus multiplication. In cell cultures, (S)-9-(3,4-dihydroxybutyl)guanine was the least active of these three drugs against a variety of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) strains. This was also the case for a certain HSV-1 or HSV-2 strain in different cell lines. In cell cultures, (R)-9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine had similar antiherpes activities. However, in vivo in cutaneous HSV-1 infections in guinea pigs treated topically and in systemic HSV-2 infections in mice treated orally or intraperitoneally, only (R)-9-(3,4-dihydroxybutyl)guanine had a therapeutic effect. The extremely short half-life in plasma and the high clearance of 9-(4-hydroxybutyl)guanine as compared with those of (R)-9-(3,4-dihydroxybutyl)guanine probably made 9-(4-hydroxybutyl)guanine inefficacious when given intraperitoneally or orally to mice infected with herpesvirus. On the other hand, no kinetic differences between (R)-9-(3,4-dihydroxybutyl)guanine and 9-(4-hydroxybutyl)guanine were observed in penetration through guinea pig skin ex vivo, and no preferential metabolism of 9-(4-hydroxybutyl)guanine in skin was noted. We deduced that high thymidine levels in guinea pig skin preferentially antagonize the antiviral effect of 9-(4-hydroxybutyl) guanine in cutaneous HSV-1 infections.

Acyclovir↗
PubMed1983

Aging and heavy drug use: a prescription survey in Manitoba.

A random sample of claimants under Manitoba's Pharmacare plan provided information on the drugs prescribed for those individuals who spent more than $50 for drugs in 1978. More women than men were represented among the 412 claimants aged 50 to 64 (58% females), and more drugs were prescribed for women than men (8.38 +/- 3.4 vs. 7.17 +/- .33, mean +/- S.E.M., p less than 0.02). For the 403 claimants aged 65 and older, the sex distribution matched that of the general population (55%), and the difference in number of drugs prescribed was not statistically significant (8.49 +/- .36 vs 7.98 +/- .35). For the claimants aged 65 and older, the five most heavily prescribed drug categories were thiazide-type diuretics (prescribed for 51.6% of older claimants in 1978), benzodiazepines (40.0%), salicylates (26.8%), digoxin (22.6%) and codeine (20.8%). There were few differences in prescription frequencies between younger and older claimants, and these data indicate that drugs prescribed for heavy drug users do not change markedly as a function of age.

Aged↗
PubMed1982

Double-blind trial of perioperative intravenous metronidazole prophylaxis for abdominal hysterectomy.

A double-blind trial of perioperative intravenous metronidazole treatment to prevent infections at the operative site and unexplained fever after abdominal hysterectomy was conducted in 106 patients. Metronidazole prophylaxis reduced the rate of recovery of anaerobes from vaginal swabs for several days and prolonged the high rate of vaginal carriage of enterococci and aerobic gram-negative bacilli following hysterectomy. Although the fever index, calculated from the duration of a temperature above 37.3 degrees C, was significantly lower in the metronidazole-treated group than in the placebo-treated group, the frequency of postoperative infections, the proportion of patients requiring antibiotic treatment and the average duration of hospital stay were similar in the two groups. These results do not support the reported value of perioperative metronidazole prophylaxis in patients undergoing abdominal hysterectomy.

Adult↗
PubMed1982

Evaluation of a human diploid cell strain rabies vaccine: final report of a three year study of pre-exposure immunization.

The antibody responses of 194 volunteers were studied for up to 3 years after primary immunization with one, two or three doses of human diploid cell rabies vaccine, administered either in 0.1 ml volumes intradermally (i.d.) or as 1.0 ml intramuscularly (i.m.). Sero-conversion occurred in 95% of subjects after the first injection and in 100% after the second. The highest titres and most durable antibody responses were induced by three injections of vaccine. Booster doses were administered either by the subcutaneous (s.c.) or i.d. route, after 6, 12 or 24 months to randomly grouped volunteers; these induced responses greater than or equal to 5.0 i.u. per ml in 95% of subjects. The responses were rapid and were neither influenced by the primary regimen nor by the timing and route of the booster dose. Antibody titres after i.d. immunization were only two-fold lower than those induced by the larger volume of vaccine. The findings suggest that the i.d. route is both effective and economic.

Adolescent↗
PubMed1979

Amantadine kinetics in healthy young subjects after long-term dosing.

We investigated the disposition of amantadine in 13 healthy, young adults after long-term dosage. Doses of 25, 100, or 150 mg, randomly allocated, were taken at 12-hr intervals in syrup for 31 doses. A 1-compartment open model and complete bioavailability were assumed. Absorption rate was variable with peak concentrations in plasma occurring at 1 to 12 hr. Since the calculated area under the plasma concentration against time curve was proprotional to it, relative bioavailability was independent of dose at steady state. As the dose increased, the apparent volume of distribution decreased. Intra- and intersubject variations in trough plasma drug concentrations at steady state were less than triple for equivalent doses. Elimination of drug from plasma was consistent with a first-order process. Plasma half-lifes (t1/2s) ranged from 10.2 to 31.4 hr and were independent of dose or creatinine clearance. The ratio of renal drug clearance to creatinine clearance ranged from 1.26 to 14.97, suggesting substantial renal tubular secretion. The median ratio of plasma drug clearance to renal drug clearance approached unity.

Adult↗
PubMed1978

Effect of a polynucleotide interferon inducer of fungal origin on experimental rhinovirus infection in humans.

A double-stranded RNA of fungal origin (BRL 5907) was given intranasally to volunteers. Apart from mild local irritancy of the higher dosage, the compound was well tolerated. A double-blind placebo-controlled trial of a three-day course (5 mg per day) of BRL 5907 against challenge with rhinovirus type 4 showed that treatment was associated with a delay in onset of symptoms and a reduction in shedding of virus, but the differences were not statistically significant. Low titers of interferon were found in nasal washings.

Adolescent↗
PubMed1978

Immunization with a human diploid cell strain of rabies virus vaccine: two-year results.

Antibody responses following primary vaccination with 1.0 ml of intramuscularly (im) or 0.1 ml of intradermally (id) administered human diploid cell rabies virus vaccine were observered for two years. Three primary doses of vaccine were given to 77 volunteers on days 0, 28, and 56. An antibody response was detected in all vacinees after a single dose; at one month, the response in the group that received vaccine id was identical to that in the group that was given vaccine im, although only 1/10th of the dose of vaccine was used. After the second and third doses, the antibody responses were higher with the primary im regimen; this difference was significant at two, three, and 12 months when the geometric mean titers of antibody were twofold higher for im than for id vaccination. The antibody responses to a booster dose of vaccine administered to randomly grouped volunteers by the subcutaneous or id route at six, 12, or 24 months were similar irrespective of the method of primary immunization but were greater with increasing intervals between primary and booster doses.

Antibody Formation↗
PubMed1976

Human diploid cell strain rabies vaccine. Rapid prophylactic immunisation of volunteers with small doses.

The clinical and antibody responses of volunteers to three intradermal schedules of human diploid cell strain rabies vaccine (0.4 ml on day 0; 0-1 ml on days 0, 1, 2, 3; and 0-1 ml on days 0, 3, 7, and 14) are described. Vaccine was administered to 114 contacts of two rabid patients in order to evoke a rapid antibody response and the antibody titres of 30 of those who were vaccinated and bled were measured. High antibody titres were obtained in all subjects irrespective of their immunisation schedule; there were only minimal local reactions. All volunteers had titres greater than 1/78 (1.7 I.U./ml) by day 14, and 7 of 10 receiving 0.1 ml into each limb on day 0 had detectable antibody by day 7.

Antibodies, Viral↗
PubMed1976

Rabies vaccines.

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Animals↗
PubMed1976

Distribution and removal of human serum albumin-technetium 99m instilled intranasally.

The efficacy of antiviral drugs and vaccines administered intranasally may depend upon the technique of application. The distribution and time-course of removal of human serum albumin-technetium 99m (HSA-Tc 99m)-instilled intranasally were studied in eleven healthy volunteers using a gamma camera and an anterior sodium iodide scintillation detector. In 100 randomized studies material was delivered as drops in the supine position or as a spray to seated subjects. A significantly higher proportion of 'good' distributions (62 in 73 tests) was obtained with drops compared with spray (1 in 27). The volume administered was varied between 0.10 ml and 0.75 ml and the concentration of HSA was changed from 3 to 30% with no significant effect upon the distribution of time-course of removal; pertechnetate in isotonic saline was distributed and removed in a manner comparable to HSA-Tc 99m. Activity recorded by the detector showed an initial rapid fall associated with removal of most of the material from the nasal cavity, followed by a slower decline associated with the removal of material mainly from the anterior region of the nose. A multidose study confirmed that frequent administration by drops is required to maintain a high level of activity in the nasal cavity. Using this technique it should be possible to correlate measurements of antiviral efficacy and vaccines take-rates with certain characteristics of intranasal applicators; such studies may lead to the design of better devices.

Administration, Intranasal↗
PubMed1975

Treatment of wounds from animals suspected of carrying neurotropic viruses.

The methods used at the Clinical Research Centre, Northwick Park Hospital, to treat wounds potentially infected with neurotropic viruses are outlined. Emphasis is laid on first aid and on surgical attention. Patients should remain under medical supervision for at least four weeks after the injury, the need for specific post-exposure treatment depending on the nature of the exposure.

Animals↗
PubMed1975

Immunogenicity and acceptability of a human diploid-cell culture rabies vaccine in volunteers.

A rabies vaccine, prepared in human diploid-cell culture, was given intradermally (i.d.) or intramuscularly (i.m.) to 35 volumteers who had not previously received prophylactic immunisation. Rabies neutralising antibody titres rose sharply after the first dose, and 4 weeks after the second dose all titres were above 1/80 (1-7 i.u. per ml.). Immunisation via the i.d. and i.m. routes was equally successful in terms of likely immune status, but the i.d. rate was associated with many more local sideeffects.

Adolescent↗