PubMed Health⌕ Search

Biomedical subjects

M L Slevin

Publications and source records attributed to M L Slevin.

At least 127 records · Page 7Linked to original sources
PubMed1984

The pharmacokinetics of subcutaneous bolus cytosine arabinoside in an arachis oil plus aluminium distearate suspension.

An attempt was made to create a delayed release preparation of cytosine arabinoside (araC) which could be administered subcutaneously, and would produce plasma levels similar to steady state infusion concentrations. A thixotropic suspension of araC in arachis oil and aluminium distearate was formulated. This preparation was similar to that previously used with bleomycin oil suspension and procaine penicillin. Two hundred mg/ml of araC in arachis oil containing varying amounts of aluminium distearate were administered firstly to New Zealand White rabbits and then to patients with acute myelogenous leukaemia. This preparation was well tolerated by both rabbits and patients but did not delay the release of araC from the subcutaneous tissues.

Animals↗
PubMed1984

High-dose cytosine arabinoside: response to therapy in acute leukaemia and non-Hodgkin's lymphoma.

Twenty-six patients with acute leukaemia and 14 with high-grade lymphoma received cytosine arabinoside (ara-C) at a twice daily dose of 2 g/m2 administered as a 3-h infusion. Thirty-four patients received 12 doses and six electively received four doses only. Complete remission was achieved in six of seven patients with acute myelogenous leukaemia (AML), one of two evaluable patients with blast crisis of chronic myeloid leukaemia and three of eight patients with acute lymphoblastic leukaemia (ALL). Three further patients with ALL had only minimal bone marrow infiltration after one cycle, toxicity precluding administration of a second. Three patients with AML who received four doses only showed no evidence of response. Four of 14 patients with lymphoma who received 12 doses, entered complete remission. Five additional patients died with minimal residual disease whilst severely neutropenic. A complete and a partial response were seen in two patients with immunoblastic and centrocytic lymphoma respectively who received four doses. These results confirm the activity of high-dose ara-C in patients with AML and suggest that it may also be a potentially useful agent in ALL and high-grade lymphoma, especially as the incidence of CNS toxicity is lower than that reported at higher doses.

Adolescent↗
PubMed1984

The efficiency of protective gloves used in the handling of cytotoxic drugs.

A range of clinical and industrial gloves have been evaluated to determine their ability to exclude penetration by cytotoxic drugs. Radiolabelled cyclophosphamide, methotrexate, daunomycin, cytosine arabinoside, and vincristine sulphate were studied in an equilibrium dialysis system in which the glove material was used as the dialysis membrane. The thicker gloves were the most effective, but very little drug crossed any of the gloves tested under laboratory conditions. Further studies to evaluate gloves in conditions of clinical use are now needed.

Antineoplastic Agents↗
PubMed1984

The bioavailability of oral intermediate-dose methotrexate. Effect of dose subdivision, formulation, and timing in the chemotherapy cycle.

The oral bioavailability of methotrexate is variable and may be dose-dependent. The absorption of 'interval' oral methotrexate, which is given between cycles of chemotherapy, is unknown. The bioavailability of oral methotrexate has been studied in eight patients, acting as their own controls, to assess the effect of subdivision of the dose, the formulation, and the timing of the methotrexate within the chemotherapy cycle. The mean bioavailability for all the oral methods of administration was 28.2% +/- 3.7% compared with the same dose given IV. Absorption was uninfluenced by subdivision of the dose, liquid or tablet formulation, or administration on day 1 or day 10 of the chemotherapy cycle.

Administration, Oral↗
PubMed1984

Delayed-release bleomycin. Comparative pharmacology of bleomycin oil suspension and bleomycin in saline.

Experimental and clinical evidence indicates that bleomycin by continuous infusion is superior to intermittent administration. Continuous infusion is less convenient, however. It has been suggested that a suspension of bleomycin in sesame oil, given by IM injection, simulates a continuous infusion. The pharmacokinetics of this formulation have been compared with those of bleomycin in saline following IM injection, in six patients. The pharmacokinetic profiles of the two formulations were similar. The only difference between the profiles was the long terminal half-life at very low concentrations between 12 and 48 h after injection of the oil suspension. This difference is of unknown, but doubtful, clinical significance.

Bleomycin↗
PubMed1984

The influence of cimetidine on the pharmacokinetics of 5-fluorouracil.

The influence of cimetidine pretreatment on the pharmacokinetics of 5-fluorouracil (5FU) has been studied in 15 ambulant patients with carcinoma. Neither pretreatment with a single dose of cimetidine (400 mg) nor with daily treatment at 1000 mg for 1 week altered 5FU pharmacokinetics. Pretreatment with cimetidine for 4 weeks (1000 mg daily) led to increased peak plasma concentrations of 5FU and also area under the plasma concentration-time curve (AUC). The peak plasma concentration after oral 5FU was increased by 74% from 18.7 +/- 4.5 micrograms/ml (mean +/- s.e. mean) to 32.6 +/- 4.4 micrograms/ml (P less than 0.05) and AUC was increased by 72% from 528 +/- 133 micrograms/ml-1 min (mean +/- s.e. mean) to 911 +/- 152 micrograms ml-1 min (P less than 0.05). After intravenous 5FU, AUC was increased by 27% from 977 +/- 96 micrograms ml-1 min (mean +/- s.e. mean) to 1353 +/- 124 micrograms ml-1 min (P less than 0.01). Total body clearance for 5FU following intravenous administration was decreased by 28% from 987 +/- 116 ml/min (mean +/- s.e. mean) to 711 +/- 87 ml/min (P less than 0.01). The elimination half-life of 5FU was not altered by cimetidine. The basis of the interaction between 5FU and cimetidine is uncertain but probably a combination of inhibited drug metabolism and reduced liver blood flow. The therapeutic implications are considerable and additional care should be taken in patients receiving the two drugs concomitantly.

Administration, Oral↗
PubMed1983

Subcutaneous infusion of cytosine arabinoside. A practical alternative to intravenous infusion.

The administration of cytosine arabinoside (araC) by continuous IV infusion requires the patient to be in hospital and have prolonged IV cannulation. In this study the pharmacokinetics of araC during continuous IV infusion were compared with those of continuous SC infusion in six patients with acute myelogenous leukaemia. Each patient acted as his own control. The mean plasma levels of araC reached a plateau within 2 h and the plasma concentrations and the area under the curve were similar for both methods of administration. The mean area under the curve (AUC) was 1147 +/- 230 ng/ml for the IV infusion and 1017 +/- 238 ng/ml for the SC infusion. The plasma araC concentrations showed wide interpatient variation, and there was also considerable variability in the plasma concentrations of araC within the individual patients after a plateau had apparently been reached. Subcutaneous infusion was well tolerated by the patients without any local discomfort or excoriation and SC infusion of araC is thus a feasible alternative to IV infusion. It allows the patients the benefits of being at home, while avoiding unnecessary thrombophlebitis.

Cytarabine↗
PubMed1983

Relationship between protein binding and extravascular drug concentrations of a water-soluble drug, cytosine arabinoside.

The degree of binding of a drug to plasma proteins has a marked effect on its distribution, elimination, and pharmacological effect. Since only the unbound fraction is available for distribution into extravascular space, the ratio of drug in cerebrospinal fluid (CSF) or saliva to that in plasma is often regarded as a physiological measure of the free fraction of a drug. CSF: plasma and saliva: plasma ratios of cytosine arabinoside (araC) have been measured in patients with acute leukaemia and found to be 0.1-0.28, implying a binding of 72-90%. The protein binding of araC was measured by equilibrium dialysis in the plasma of patients with acute leukaemia at presentation. The mean binding ratio was 2.3 +/- 6.8, implying that there was little or no protein binding. There was no correlation between alpha-1 acid glycoprotein (AAG) levels and protein binding. The low CSF and saliva: plasma araC ratios found, suggest that drugs such as araC which have low lipid solubility do not pass freely into extravascular space. Thus the CSF or saliva: plasma ratio cannot be considered a good physiological measure of protein binding for drugs with poor lipid solubility.

Blood Proteins↗
PubMed1983

Effect of dose and schedule on pharmacokinetics of high-dose cytosine arabinoside in plasma and cerebrospinal fluid.

The pharmacokinetics of high-dose cytosine arabinoside (ara-C) were studied in 18 patients with acute leukemia and high-grade non-Hodgkin's lymphoma. The plasma concentrations of ara-C increased in proportion to the dose over a range of 1-3 g/m2. The initial and terminal half-lives were not influenced by the dose or schedule of administration and no accumulation of ara-C occurred with repeated dosage in the same patients. These data suggest that cytidine deaminase is not saturated within this dose range. The cerebrospinal fluid (CSF) concentrations of ara-C also rose linearly with the increase in dose and varied from 347 ng/mL (1 g/m2) to 1,070 ng/mL (3 g/m2). The mean CSF concentrations of ara-C following high-dose infusions over three hours were 6%-22% of simultaneous plasma concentrations. Three hours after completion of the intravenous infusion the CSF concentrations were greater than the corresponding plasma concentrations owing to the long half-life of ara-C in CSF compared to that in plasma. These data demonstrate that therapy with intravenous high-dose ara-C given twice daily provides continuous levels in the CSF at concentrations that are likely to be of value in the treatment of central nervous system leukemia.

Cytarabine↗
PubMed1983

Small-cell lung carcinoma: survival after combination chemotherapy, radiotherapy or symptomatic treatment.

A retrospective comparison was made of the survival of patients with small-cell lung carcinoma treated by combination cytotoxic chemotherapy (CT), radiotherapy (RT) or symptomatic therapy alone (ST). Forty-three patients received CT and 42 patients of similar age and performance status each received RT or ST at the same group of hospitals. The median survival was 43 weeks with CT, 18 weeks with RT and 6 weeks with ST and 1 year survivals of 36%, 12% and 8% respectively were obtained. Despite the limitations of a retrospective study these results suggest that an improved survival with toxicity acceptable to most patients results from cytotoxic chemotherapy.

Adult↗
PubMed1982

Short-term treatment for acute myelogenous leukaemia.

Short-term treatment with doxorubicin, cytarabine, and 6-thioguanine was given to 91 consecutive adults with acute myelogenous leukaemia. Fifty patients received high doses (regimen I) and 41 very high doses (regimen II). Where possible, six treatment cycles were given (total dose of doxorubicin 450 mg/m2) regardless of the number of cycles required to achieve complete remission. No additional treatment was given. The remission rate was significantly higher with regimen I than with regimen II (34/50 compared with 15/41, p less than 0.01), the latter, more intensive regimen being associated with a greater incidence of fatal infection (13/41 compared with 5/50, p less than 0.01). Duration of remission was, however, significantly longer with regimen II (p less than 0.05); the median has not yet been reached after a minimum follow-up of two years. Intensive short-term treatment is a feasible strategy for the treatment of acute myelogenous leukaemia.

Adolescent↗
PubMed1982

A comparison of two schedules of cytosine arabinoside used in combination with adriamycin and 6-thioguanine in the treatment of acute myelogenous leukemia.

The most effective schedule of cytosine arabinoside (Ara-C) administration remains controversial and is further confused by the use of combination chemotherapy. Two remission induction regimens comprising adriamycin, Ara-C, and 6-thioguanine have been compared in patients with acute myelogenous leukemia. Administration of Ara-C by continuous intravenous infusion resulted in faster clearing of leukemic blasts from the peripheral blood and bone marrow than after administration of the same dose by twice daily intravenous injection. Myelosuppression and gastrointestinal toxicity were, however, more pronounced when Ara-C was given by infusion. The complete remission rate was higher in the patients treated with intravenous infusions. It is too early to assess the duration of remission in the infusion study; however, despite the relatively low remission rate, 80% of patients under the age of 60 in the intravenous bolus study remain in remission with a minimum follow-up of two years.

Adult↗