Biomedical subjects

T MacGregor

Publications and source records attributed to T MacGregor.

6 recordsLinked to original sources

PubMed2006

Serum 25-hydroxyvitamin D levels in early and advanced breast cancer.

BACKGROUND: Laboratory and epidemiological studies have implicated vitamin D deficiency in the pathogenesis of breast cancer. 1,25-Dihydroxyvitamin D (1,25(OH)(2)D) promotes differentiation and apoptosis, and potently inhibits proliferation of malignant breast epithelial cells in culture. Serum levels of 1,25(OH)(2)D are higher in normal women than in patients with primary breast cancer. AIM: To clarify the role of vitamin D in breast cancer progression by comparing the levels of serum vitamin D in patients with early and in those with advanced breast cancer. METHODS: Circulating levels of 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium were measured prospectively in 279 Caucasian women with invasive breast cancer, 204 women with early-stage disease and 75 women with locally advanced or metastatic disease. RESULTS: Patients with early-stage breast cancer had significantly higher circulating levels of 25(OH)D (p<0.005) and significantly lower PTH (p<0.001) levels than those with advanced disease. Calcium levels did not differ significantly (p = 0.74). CONCLUSION: Serum levels of 25(OH)D are significantly higher in patients with early-stage breast cancer than in those with locally advanced or metastatic disease.

Adult↗

PubMed1999

Disposition and biotransformation of the antiretroviral drug nevirapine in humans.

The pharmacokinetics and biotransformation of the antiretroviral agent nevirapine (NVP) after autoinduction were characterized in eight healthy male volunteers. Subjects received 200-mg NVP tablets once daily for 2 weeks, followed by 200 mg twice daily for 2 weeks. Then they received a single oral dose (solution) of 50 mg containing 100 microCi of [(14)C]NVP. Biological fluids were analyzed for total radioactivity, parent compound (HPLC/UV), and metabolites (electrospray liquid chromatography/mass spectroscopy and liquid chromatography/tandem mass spectroscopy). Mean recovery of radioactivity was 91.4%, with 81.3% excreted in urine and 10.1% recovered in the feces over a period of 10 days. Circulating radioactivity was evenly distributed between whole blood and plasma. At maximum plasma concentration, parent compound accounted for approximately 75% of the circulating radioactivity. Mean plasma elimination half-lives for total radioactivity and NVP were 21.3 and 20.0 h, respectively. Several metabolites were identified in urine including 2-hydroxynevirapine glucuronide (18.6%), 3-hydroxynevirapine glucuronide (25.7%), 12-hydroxynevirapine glucuronide (23.7%), 8-hydroxynevirapine glucuronide (1.3%), 3-hydroxynevirapine (1.2%), 12-hydroxynevirapine (0.6%), and 4-carboxynevirapine (2.4%). Greater than 80% of the radioactivity in urine was made up of glucuronidated conjugates of hydroxylated metabolites of NVP. Thus, cytochrome P-450 metabolism, glucuronide conjugation, and urinary excretion of glucuronidated metabolites represent the primary route of NVP biotransformation and elimination in humans. Only a small fraction of the dose (2.7%) was excreted in urine as parent compound.

Adult↗

PubMed1995

Product characteristics and pharmacokinetics of intranasal ipratropium bromide.

The in vivo absorption potential of ipratropium bromide nasal spray was evaluated in studies involving healthy volunteers (0.03%, 0.06%, and 0.12% dosage strengths) and patients with perennial rhinitis (0.03% and 0.06%) and the common cold (0.06%). The dose used was two sprays per nostril, corresponding to a total dose of 84 micrograms, 168 micrograms, and 336 micrograms for the three dosage strengths. These studies indicate that 10% or less of active drug is absorbed systemically after nasal administration based on the amount of unchanged drug excreted in urine in a 24-hour interval. In most instances, the plasma drug concentrations were undetectable. In none of these studies did plasma ipratropium concentrations reach a level where systemic anticholinergic effects are known to occur.

Absorption↗

PubMed1994

Argon Assisted CO2 Laser Laparoscopy

The use of a small amount of Argon gas to purge the operating channel of the CO2 laser laparoscope eliminates the thermal lensing (blooming) that has plagued CO2 laser laparoscopy. By eliminating the blooming, the power density and transmission of laser power is increased. Overall, the efficacy of the CO2 laser/laparoscope system is dramatically improved. This simple procedure allows even older CO2 lasers to equal the efficiency of the newer generation shifted wave length CO2 isotope lasers. This technique is superior to others which require special equipment to achieve extremely high insufflation/evacuation flow rates in order to control thermal blooming.

Journal Article↗

PubMed1990

Oral pharmacokinetics of pirenzepine in patients with chronic renal insufficiency, failure, and maintenance haemodialysis.

The pharmacokinetic properties of pirenzepine following administration of a single, 50 mg oral dose were evaluated in three groups of subjects: group I, end stage renal disease requiring maintenance haemodialysis (CLCR 0 to 10 ml.min-1); group II, moderate renal insufficiency (CLCR 10 to 30 ml.min-1); and group III, mild renal dysfunction (CLCR 30 to 70 ml.min-1). Additionally, subjects in group I received a 50 mg dose on a non-dialysis day and at least one week later, a 50 mg dose during haemodialysis. There was a linear relationship (r = 0.97) between pirenzepine renal clearance and renal function as measured by creatinine clearance. The harmonic mean terminal half-life for pirenzepine was 17.3 h in subjects with end stage renal disease, 18.0 h in subjects with moderate renal insufficiency and 14.7 h in subjects with mild renal dysfunction. Haemodialysis reduced the level of circulating pirenzepine by approximately 25%. The mean arterial to venous plasma pirenzepine ratio during hemodialysis was 1.29 (range 1.02-1.56). Based on subjective reporting of adverse experiences and clinical observation, pirenzepine appeared to have had a wide margin of safety in these patients. Dry mouth was the most frequently reported adverse experience attributable to pirenzepine administration. A reduction in dose or dosing frequency may be warranted only in end state renal disease (CLCR 0 to 10 ml.min-1).

Administration, Oral↗

PubMed1986

Relative bioavailability of metaproterenol in humans utilizing a single dose, stable isotope approach.

The relative bioavailability of metaproterenol (3,5-dihydroxy-alpha-[(isopropylamino)methyl]benzyl alcohol) following a single dose (10-mg metaproterenol sulfate tablet) was studied in six normal male volunteers using coadministration of a solution of a deuterated analogue (metaproterenol-d7 sulfate). The bioavailability of the tablet formulation relative to that of the oral solution was 92 +/- 9%, with excellent power at the 5% significance level. Comparison of the coadministration of the labeled and unlabeled metaproterenol sulfate solutions in two subjects after a one-week washout demonstrated the absence of an isotope effect on either absorption or elimination. A GC-MS assay for metaproterenol was developed to measure plasma concentrations resulting from oral administration. The assay was linear over the range of 0.5-8 ng/mL, corresponding to typical plasma metaproterenol concentrations obtained after a single 10-mg oral dose. Accuracy and precision data were obtained at metaproterenol concentrations of 1.0 and 2.0 ng/mL plasma to demonstrate the applicability of the assay for bioavailability studies. Following oral administration, metaproterenol showed peak plasma concentrations of 2.2 to 13 ng/mL at 0.75 to 3.0 h, with a terminal harmonic mean half-life of 2.1 h over the plasma concentration range studied. The renal clearance of 133-158 mL/min for metaproterenol slightly exceeds the glomerular filtration rate in humans.

Administration, Oral↗