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At least 19 recordsLinked to original sources
PubMed1992

[Drug administration schedules in geriatric patients].

BACKGROUND: In this study the prescription of drugs in an outpatients geriatric population was evaluated in terms of age and body weight. METHODS: From a wide survey carried out on 500 geriatric outpatients, all the prescriptions corresponding to H-2 antagonists, digoxin, theophylline, bromazepam, diazepam, lorazepam and triazolam were analyzed. The patients studied were of 60 or more years of age. For each drug patients were stratified into groups according to intervals of body weight with mean age of the patient being determined in each of the intervals as well as the doses received in mg/kg. RESULTS: Two hundred eighty prescriptions were analyzed with 12% corresponding to the H-2 antagonists, 29% to digoxin, 23% to theophylline and 35% to benzodiazepines. There was no significant correlation between age and the doses received. In general, the lowest body weight corresponded with a higher mean age and a marked increase in the mean dose of cimetidine, ranitidine, theophylline, bromazepam, lorazepam, and triazolam administered. There was a tendency to an adjustment in the doses of digoxin in the most elderly patients. CONCLUSIONS: The data found concerning the prescription of drugs to a geriatric outpatients population indicate that in elderly patients adjustments are not made in the doses of drugs administered according to the age and body weight of the patient. Low body weight of the elderly is a overdosage risk factor.

Age Factors↗
PubMed1977

Barbiturate dependence in mice: effects of continuous vs. discontinuous drug administration.

Three groups of DBA/2J mice were continuously exposed for 3, 6 or 9 days to a milled diet containing phenobarbital. Two additional groups were given a discontinuous drug administration schedule with either one or two 24 h drug-free periods interpolated among the 6 or 9 days of phenobarbital consumption, respectively. The discontinuous schedule of drug administration significantly attenuated the development of physical dependence as determined by the severity of withdrawal symptoms. Functional tolerance development was also attenuated in a manner that closely paralleled the effects on physical dependence development. The 5 group means showed a perfect rank order correlation between functional tolerance and physical dependence development.

Animals↗
PubMed1979

Dacarbazine and melphalan. Enhancement by dosage scheduling of the effect in combination treatment on the Harding-Passey melanoma in C3D2F1 mice.

The best combination and schedule for dacarbazine and melphalan with the Harding-Passey melanoma in C3D2F1 mice is achieved when dacarbazine is administered first, followed by melphalan, given on either the day of dacarbazine therapy or the first three days after dacarbazine is given. When dacarbazine is given first, followed by melphalan on day 0, 1, 2, or 3, the effect of the two drugs is considerably more than additive. Other schedules reduce the outcome to a simple additive effect, or to an outcome that is less than additive, in which the combination is less effective than melphalan used alone. The effect of variations in the order and schedule of drug administration should be investigated in future trials of cancer chemotherapeutic agents, since profound effects may occur with these variations.

Animals↗
PubMed1978

Phase 1 clinical investigation of 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992), a new acridine derivative.

The compound 4'-(9-acridinylamino)methanesulfon-m-anisidide is a new derivative that was evaluated in a Phase 1 clinical trial. The schedule of drug administration consisted of daily i.v. injection for 3 consecutive days, repeated at 3-week intervals. Twenty-six patients received a total of 63 courses of 4'-(9-acridinylamino)methanesulfon-m-anisidide in a dose range from 4 to 50 mg/sq m/day. Hematopoietic toxicity was dose limiting, but it was of short duration and rapidly reversible. Mild nausea and vomiting were observed in 16% of the courses, and a mild degree of phlebitis was observed in 10% of the courses. Responses were observed in two patients with adenocarcinoma of the lung and one each of melanoma and acute myeloblastic leukemia. Phase 2 studies of 4'-(9-acridinylamino)methanesulfon-m-anisidide are planned at a starting dose of 40 mg/sq m/day for 3 days in good-risk patients and at 25 to 30 mg/sq m/day for 3 days in poor-risk patients. Course of treatment would be repeated at 21-day intervals.

Acridines↗
PubMed1977

Interaction of antitumor agents including doxorubicin or daunorubicin in sarcoma-180 system.

Combination effect of antitumor agents, including doxorubicin and daunorubicin, was evaluated on the concept of pharmacological synergism in ascites sarcoma-180 system. In alternate adminsitration, combinations of doxorubicin plus cyclophosphamide, thio-TEPA, carboquone, actinomycin-D, vinblastine, vincristine, methotrexate, cytarabine, 6-mercaptopurine, or L-asparaginase showed synergism, but in simultaneous one, only three agents, cyclophosphamide, carboquone, and cytarabine, were synergistic. On the other hand, combination of daunorubicin plus one of 8 agents (thio-TEPA, mitomycin-C, bleomycin, actinomycin-D, vinblastine, ancytabine, 6-mercaptopurine, and L-asparaginase) and 6 agents (cyclophosphamide, thio-TEPA, mitomycin-C, bleomycin, actinomycin-D, and vinblastine) provided synergism in alternate and simultaneous administration. Combination effect of agents was affected by the schedule of drug administration for doxorubicin, but weak for daunorubicin. Toxicity of doxorubicin or daunorubicin in combination with other drugs was also affected by the schedule of administration. Combination of a larger number of agents in simultaneous administration provided antagonism compared with an alternate administration.

Animals↗
PubMed1975

Some thoughts on experimental screening.

Experimental screening of anticancer drugs is discussed from the standpoint of the need for close co-operation between experimentalists and clinicans in developing therapies for human trials. Particular emphasis is given to screening analogues of known active drugs including the approaches in chemical synthesis and tests of experimental tumor activity, as well as the questions that determine clinical interest and capabilities for human trials. In the area of combinations of two or more drugs, the need for experimental systems providing data for rational design of clinical regimens is highlighted. Means for experimental evaluation of the major variables of dose ratio, dose schedule and sequence of drug administration are considered. Finally, the overall problems of drug screening are discussed within the context of combining drugs with other treatment modalities, such as surgery, radiotherapy, and immunotherapy. The complexities of designing better cancer treatment will require close interaction between experimental and clinical studies.

Animals↗
PubMed1979

Podophyllotoxin derivative VP 16-213.

VP 16-213, a derivative of podophyllotoxin, is currently entering phase-III studies. Its mode of action is incompletely understood, but differs markedly from that of its parent compound. The greatest lethal damage is experienced by cells in the late S and G2 phases. In the L 1210 system the drug shows marked schedule dependency: prolonged administration may be more effective than single bolus administration. As a single agent, VP 16-213 is the most active compound yet tested against small-cell bronchial carcinoma. It may also prove to be a useful agent in patients with other types of lung tumour, testicular teratomas, and some types of leukaemia. No long-term or cumulative toxicity has been reported. Most side effects are predictable and reproducible.

Animals↗
PubMed1976

Effect of short- and long-term administrations of some drugs on rat intestinal flora. Short communication.

Two schedules of treatment were adopted for an experimental evaluation of drug induced alterations in mid-small intestinal flora of normal rats. Test substances were given orally twice daily for 3 days at large doses and once daily for 30 days at lower doses. Indometacin, benzydamine, phenylbutazone, pheprazone, picosulfol, magnesium sulfate, tolbutamide, phenformin, dexamethasone acetate and prednisolone acetate were tested. Drug-induced alterations in rat intestinal flora resulted more evidently following multiple short-time treatments.

Administration, Oral↗
PubMed1977

Metabolism of 5-hydroxytryptamine and levels of tricyclic antidepressant drugs in rat brain after acute and chronic treatment.

Because tricyclic antidepressants (TAD) are usually given chronically to patients, both their acute and their chronic effects on 5-hydroxytryptamine (5-HT) metabolism were studied. The probenecid method was used and, in addition to 5-hydroxy-indoleacetic acid (5-HIAA), some other indole compounds in brain were measured. Simultaneously, TAD levels in brain and plasma were determined. Dimethylated as well as monomethylated TADs were administered, both at 10 and 25 mg/kg i.p. Treatment with either 10 mg/kg during 14 days or 25 mg/kg given acutely resulted in a similar brain level of TAD, so any differences found could be attributed to differences in administration schedule. Drug levels in brain and plasma differed considerably after chronic and acute treatments but no major differences in the effect on 5-HIAA level in the brain were found, although accumulation of 5-HIAA following probenecid treatment was mostly lowered after treatment with dimethylated TAD. The TAD level in rat brain was not decisive for the effect on central 5-HT turnover. The monomethylated TAD affected the 5-HT turnover very little, not only acutely but also chronically.

Animals↗
PubMed1977

Adjuvant postoperative chemotherapy with 5-fluorouracil and methotrexate: effect of schedule of administration on metastasis of 13762 mammary adenocarcinoma.

Metastasizing mammary adenocarcinoma 13762 in female Fischer rats has been used as a model for studying postoperative adjuvant chemotherapy, using methotrexate (Mtx) and 5-fluouracil (5FU) either singly or in combinations. All animals that received postoperative adjuvant chemotherapy of 5FU alone, 5FU and Mtx simultaneously, or Mtx followed by 5FU had significant improvement of survivals. Methotrexate alone was ineffective in treating the visceral metastasis. The addition of Mtx at the time of 5FU administration actually decreased the therapeutic effectiveness of 5FU given by itself. Fluorouracil alone improved survival of rats with small or large tumors, whereas Mtx followed by 5FU was better than 5FU alone in rats with smaller tumors. Among all rats treated with chemotherapy, those rats that got Mtx followed by 5FU had the lowest amount of lung metastasis, and concomitant administration of nonspecific BCG immunotherapy delayed death from visceral metastasis only for rats receiving drugs according to this schedule.

Adenocarcinoma↗
PubMed1977

Antipsychotic drug use: physician prescribing practices in relation to current recommendations.

Forty-two Veterans Administration hospitals contributed data on all the psychotherapeutic drugs being prescribed for a sample of their patients. These prescriptions were compared with the recommendations in "Guidelines for Antipsychotic Drug Use" by Drs. Prien and Caffey (1975). Generally, the results showed moderate differences between the actual physician practices and those recommended in the guidelines. The most significant differences were in polypharmacy, use of antiparkinson drugs, dosage levels and "drug holidays". The use of once- or twice-a-day schedules and the administration of major portion of the dose at night were much closer to the recommendation.

Antiparkinson Agents↗
PubMed1976

Deveopment of resistance to combinations of six antimetabolites in mice with L1210 leukemia.

The development of resistance to combinations of 6-mercaptopurine, 6-thioguanine, 6-methylmercaptopurine riboside, methotrexate, 5-fluorouracil, and cytosine arabinoside was studied in L1210 leukemia through 60 transfer generations. The treatment schedules were either simultaneous or offset. In simultaneous administration, one sixth of the LD10 of each of the six drugs was administered within a few minutes, daily for 6 days. In offset administration, the drugs were given either in the above-listed order or in reversed order, with one drug given each day. In the simultaneous combination treatment protocol 31 transfer generations were necessary to reach partial resistance, but in the two offset combination schedules only five and three generations were needed. The relative rate of development of resistance to the individual drugs was slower in the three combination schedules than in single-drug schedules. Resistance to 6-mercaptopurine and 6-thioguanine was completed after four generations on the offset combination schedules, but only after 28 generations on the simultaneous schedule.

Animals↗
PubMed1978

Treatment of essential hypertension with pindolol.

Pindolol was given for 12-15 consecutive weeks to 35 patients for the treatment of essential hypertension. Significant blood pressure reductions were achieved in the group of 28 patients who completed the trial, as tested by the Wilcoxon pair test. There was no difference in antihypertensive effect between a three times a day and a twice a day administration schedule. The incidence of side-effects was not affected by the change in dosage or schedule.

Adult↗
PubMed1992

Phase II trial of fazarabine in advanced colorectal carcinoma.

A total of 15 patients with measurable advanced colorectal adenocarcinoma were prospectively treated with fazarabine (Ara-AC), reconstituted in dimethyl sulfoxide, and administered at a starting dose of 48 mg/m2/day as a continuous intravenous infusion for three days. The dose was repeated every 21 days and dose escalations or reductions were made on the basis of toxicities encountered in the preceding course. No patient achieved either a complete or partial response. Major toxicities encountered were granulocytopenia, thrombocytopenia, nausea, vomiting, anemia, and headache. All toxicities were reversible upon discontinuation of the drug and no life-threatening toxicities occurred. These data indicate that further clinical trials in colorectal carcinoma with this agent and schedule of administration are not warranted.

Adult↗