Single-dose administration of Bowman-Birk inhibitor concentrate in patients with oral leukoplakia.

The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor and a potential cancer chemopreventive agent for humans. In this Phase I clinical trial, BBI concentrate was administered as a single oral dose to 24 subjects with oral leukoplakia. Pharmacokinetics of BBI was analyzed, and subjects were monitored clinically for toxic effects.

Phase I/II trial of human recombinant granulocyte-colony-stimulating factor (filgrastim) and escalating doses of cyclophosphamide, mitoxantrone, and 5-FU in the treatment of advanced breast cancer.

Purpose: We performed a phase I/II dose-escalation trial of cyclophosphamide, mitoxantrone, and 5-fluorouracil (CNF) in combination with human recombinant granulocyte-colony-stimulating factor (G-CSF, filgrastim) in patients with advanced breast cancer. The objectives of this trial were (1) to gain experience with filgrastim given to patients with advanced breast cancer and receiving standard-dose CNF, and (2) to determine the maximum tolerated dose of CNF that could be given with filgrastim support by incremental dose escalation of two components of the CNF regimen, cyclophosphamide and mitoxantrone.

Methods: Four patients who had received prior therapy for advanced disease received standard-dose CNF with filgrastim support.

Restoration of oral all-trans retinoic acid bioavailability after a brief drug holiday.

We evaluated the utility of a 7-day drug holiday in the restoration of chronic dosing all-trans-retinoic acid (tRA) blood levels in 11 non-small cell lung carcinoma patients. Baseline kinetic studies (day 1) were compared to postchronic dosing (day 7) and drug holiday kinetics (day 14). High levels of baseline pharmacokinetic variability and variability in response to prolonged tRA therapy were evident.

A phase II trial of a differentiating agent (tRA) with cisplatin-VP 16 chemotherapy in advanced non-small cell lung cancer.

The prognosis for advanced non-small cell lung cancer remains poor. Response to chemotherapy is infrequent and overall survival is low. Trans-retinoic acid (tRA), a differentiating agent whose mechanism of action is thought to be different from conventional chemotherapy has activity in preclinical models and low but definite activity in the clinical setting.

Levels of proteolytic activities as intermediate marker endpoints in oral carcinogenesis.

It is essential to identify intermediate marker endpoints of carcinogenesis for the evaluation of the effectiveness of cancer-chemopreventive agents. We have observed that levels of proteolytic activities (as detected by 4 different substrates) are increased 2-3-fold (P < 0.003) in oral buccal mucosa cells of smokers and patients with oral leukoplakia or erythroplakia as compared to a nonsmoking comparison group.

Phase II evaluation of mitoxantrone plus cis-platinum in patients with advanced breast cancer. A Southwest Oncology Group study.

The Southwest Oncology Group studied the response rate and toxicity of mitoxantrone (7.5 or 10 mg/m2 to 12.0 mg/m2) and cis-platinum (100 mg/m2) in 30 patients with advanced breast cancer as second-line therapy.

Effects of ketoconazole on the polymorphic 4-hydroxylations of S-mephenytoin and debrisoquine.

Studies were undertaken in 12 normal, male subjects to determine whether a metabolic interaction occurs between ketoconazole and mephenytoin. A single dose (400 mg) of ketoconazole produced a reduction in the 0-8 h urinary R/S ratio of mephenytoin following oral administration (100 mg) of racemic drug and after 28 daily doses the median value was further reduced to 42.9% of its baseline value.

Effect of etomidate on hepatic drug metabolism in humans.

The authors studied the effect of etomidate on drug metabolism in vivo in humans and in vitro using human liver microsomes. When these liver microsomes were incubated with different concentrations of etomidate, dose-dependent inhibition of ketamine N-demethylation, a cytochrome P-450-dependent enzymatic process, was produced. Cytochrome P-450 binding spectra displayed type II binding with a UV light absorption maximum (lambda max) at a wavelength of 424 nm in the presence of etomidate.

Rhabdomyolysis complicating doxylamine overdose.

A 16-year-old male presenting with anticholinergic symptoms was found to have hematuria and oliguria. Evaluation of the patient revealed a serum creatinine of 2.2 mg/dl, myoglobinuria, and a creatine phosphokinase (CPK) level of 78, 750 IU/l with 99 percent fraction 3 isoenzyme.

Plasma antipyrine half-life can be determined from urine data.

Antipyrine half-life has been determined from measurements of antipyrine concentrations in spontaneously voided urine specimens in eleven subjects, studied on a total of forty-seven different occasions while receiving no drugs, interferon or ketoconazole. Plasma and saliva half-lives show good intrasubject correlation. Plasma and urine half-lives show good intrasubject correlation provided total urine output is at least 1.

Acute poisoning in the emergency room in Lagos University Teaching Hospital.

This paper reviews 146 cases of acute poisoning seen and treated by us at the adult accident and emergency centre of Lagos University Teaching Hospital, Nigeria, between 1979 and 1982. Barbiturates (19%) and benzodiazepines (17%) were the commonest drugs used in acute poisoning. The highest incidence (41%) was found among persons aged 18-25 years.