Usage patterns of transdermal nicotine when purchased as a non-prescription medicine from pharmacies.

OBJECTIVE: To assess nicotine patch use in smokers who purchased the product as a non-prescription medicine from pharmacies. DESIGN: A questionnaire administered at the time of purchase. SETTING: Community pharmacies throughout New Zealand. SUBJECTS: A total of 805 male and female purchasers of nicotine patches aged 18 through 87 years. MAIN OUTCOME MEASURES: Patterns of usage including self-reported smoking history, previous quit-smoking attempts, previous and current use of transdermal nicotine and other products, side effects, and concomitant smoking. RESULTS: Most respondents (74%) had attempted to quit smoking previously, many of whom (53%) had used a non-prescription nicotine replacement product. Approximately 60% of purchasers were first-time users. For those continuing a course of treatment, there was no evidence of use for longer than the manufacturer's recommendation (12 weeks). Twenty-eight per cent of respondents reported continuing smoking while using transdermal nicotine, although the number of cigarettes smoked was much less than in the reported smoking history. Side effects were reported by 24% of patch users in the current course, but there was no evidence of significant safety problems. CONCLUSIONS: This survey provides preliminary data on the non-prescription usage of transdermal nicotine when purchased through pharmacies.

Effects of capsaicin on the pharmacokinetics of antipyrine, theophylline and quinine in rats.

Capsaicin is the active principal of capsicum fruits, such as hot peppers. The influence of 1-week pretreatment of capsaicin (25 mg kg-1) on the pharmacokinetics of antipyrine, theophylline and quinine was investigated in rats. The drugs were given as an intravenous bolus dose. The control rats received the vehicle solvent (polyethylene glycol) only. Clearance of antipyrine in the capsaicin-pretreated rats was significantly lower than that observed in the control rats (0.241 +/- 0.029 vs 0.344 +/- 0.034 L h-1 kg-1, P < 0.05). This is consistent with a prolongation in the elimination half-life of antipyrine in animals pretreated with capsaicin (2.06 +/- 0.30 vs 1.61 +/- 0.27 h), as the volume of distribution was not significantly changed. In contrast, capsaicin pretreatment had no significant effect on the pharmacokinetics of theophylline and quinine.

Pharmacokinetics of pirmenol in young and elderly subjects.

The steady state pharmacokinetics of pirmenol was compared in twelve healthy young (aged 18 to 45 y) and 11 elderly subjects (over 65 y) subjects given pirmenol HCl 100 mg every 12 h for a total of 14 doses. In addition, the single-dose pharmacokinetics of pirmenol was determined following a 100 mg oral dose in the young subject group for comparison with the results of repeated administration. In the young subjects, the mean single-dose and steady-state CLR of pirmenol were similar; however, Ae was 29% higher and CL/f was 22% lower at steady state than after the single dose. Steady-state (fourteenth dose) Cmin, Cmax, tmax, lambda z, Ae, CL/f, CLR and V values were similar in the young and elderly subjects. Based on pharmacokinetic considerations, the dosage of pirmenol is unlikely to differ in young and elderly subjects.

Enhanced elimination of piroxicam by administration of activated charcoal or cholestyramine.

This study has compared the effect of repeated administration of charcoal and cholestyramine on the elimination of piroxicam. Eight young adults were given piroxicam as a single dose of 20 mg, on 3 separate occasions. On one of the occasions charcoal was also given. On another occasion cholestyramine was also administered. The mean elimination half-life after piroxicam alone was 53.1 h. This was reduced to 40.0 h by charcoal administration and to 29.6 h after administration of cholestyramine. In the second phase of the study 7 elderly subjects received piroxicam 20 mg for 14 days on two occasions. Cholestyramine administration at the end of one of the periods reduced the mean elimination half-life of piroxicam from 52.3 h to 27.3 h.

Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein.

alpha 1-Receptor antagonists and antidepressant agents are basic (cationic) drugs that are known to bind to alpha 1-acid glycoprotein (AAG). Since these drugs are frequently co-administered and since they bind to the same protein, this investigation was designed to evaluate the "in vitro" ability of antidepressants, alpha 1-receptor antagonists, and propranolol to displace [3H]imipramine and [3H]prazosin from the AAG binding site(s). Equilibrium dialysis was employed. Of the drugs studied, the following order of potency in displacing [3H]prazosin was found: trazodone greater than prazosin greater than doxazosin greater than propranolol greater than doxepin = amoxapine = trimazosin = amitriptyline greater than imipramine greater than nortriptyline = desipramine = nomifensine greater than bupropion = maprotiline. [3H]lmipramine binding from AAG was displaced with the following potency order: prazosin greater than imipramine greater than propranolol greater than doxazosin greater than nortriptyline greater than desipramine greater than trimazosin. Tricyclic antidepressants produced similar degrees of displacement of both [3H]imipramine and [3H]prazosin from AAG; whereas, alpha 1-receptor antagonists were more effective displacers of [3H]prazosin than of [3H]imipramine. Furthermore, the demethylated metabolites of imipramine and amitriptyline were less potent displacers than their parent compounds. These results suggest that more than a single binding site may be available for binding to AAG and that hydrophobic bonding is important in the binding of drugs to AAG.

Analysis of 5'-deoxy-5-fluorouridine and 5-fluorouracil in human plasma and urine by high-performance liquid chromatography.

A relatively simple and sensitive high-performance liquid chromatographic (HPLC) method is described for measuring the two anticancer drugs 5'-deoxy-5-fluorouridine (5'dFUR) and 5-fluorouracil (5-FU) in human plasma and urine. The procedure for plasma includes solvent extraction using ethyl acetate-isopropyl alcohol (85:15) followed by silica gel column chromatography to separate these compounds from constituents normally occurring in plasma. The analysis by reversed-phase HPLC is performed on a phenyl column using an aqueous mobile phase with ultraviolet detection (280 nm). The overall recovery from plasma was 61% and 65% for 5'dFUR and 5-FU, respectively. The sensitivity limit of the assay for both compounds was 50 ng/ml of plasma. Analysis of these compounds in urine did not require the silica column chromatography isolation step.

Pharmacokinetic projections for isoxicam and piroxicam in old and young subjects.

A single-dose pharmacokinetic study to determine the effect of age on the disposition of isoxicam and piroxicam was carried out on a group of old and a group of young subjects. Although there was no significant difference with either drug in the mean elimination half-time between the group of young and the group of old subjects, there was considerable individual variation. Steady-state levels were calculated to be three times as high in subjects with slow clearance as in those with more rapid clearance. Three weeks would be required with either drug to achieve steady-state drug levels in those subjects with slow drug-clearance.

Factors affecting the kinetics of two benzothiazine non-steroidal anti-inflammatory medicines, piroxicam and isoxicam.

The pharmacokinetics of isoxicam and piroxicam were compared in 12 young adults (less than 40 years) and 12 elderly subjects (greater than 65 years). After a single oral dose of 200 mg isoxicam or 20 mg piroxicam blood samples were taken for 168 h and the plasma drug concentrations determined by HPLC. The elimination half life of piroxicam for the adults was 57.1 +/- 16.4 h (mean +/- SD; harmonic mean 52.9 h) and for the elderly subjects was 57.8 +/- 22.1 h (harmonic mean 52.1 h). The corresponding values after isoxicam were 34.3 +/- 13.6 h (harmonic mean 31.6) for the adults and 39.1 +/- 22.7 h (harmonic mean 33.5) for the elderly subjects. Similarly no differences were noted in either the AUC0-infinity after piroxicam (adults 154.1 +/- 52.2 micrograms . h/ml, elderly 163.6 +/- 99.1 micrograms . h/ml) and isoxicam (adults 642.7 +/- 241.9 micrograms . h/ml, elderly 787.9 +/- 613.1 micrograms . h/ml) or the apparent oral clearance of piroxicam (adults 2.39 +/- 0.80 ml/min, elderly 2.51 +/- 0.90 ml/min) and isoxicam (adults 5.84 +/- 2.04 ml/min, elderly 5.59 +/- 2.12 ml/min). One adult and two elderly subjects exhibited slower elimination of both medicines than the remainder of each group. However determination of the oxidation phenotype using sparteine metabolism showed that this was not a likely determinant of the reduced clearance.

Bioavailability of metoprolol in young adults and the elderly, with additional studies on the effects of metoclopramide and probanthine.

The bioavailability of metoprolol was studied in eight healthy young and seven healthy elderly volunteers. Large interindividual differences in the bioavailability of metoprolol were observed in both groups. However, there was no significant difference in AUC, peak plasma concentration or elimination half-life between young and elderly, but time to peak concentration was significantly longer in the elderly. Pretreatment with metoclopramide had no effect on AUC but caused significant increases in peak concentration and decreases in time to peak concentration in both groups. Probanthine pretreatment (only to the young) resulted in a significant decrease in peak concentration of metoprolol and a significant increase in time to peak concentration but had no effect on the AUC. These results suggest that alterations in gastric emptying and gut motility due to ageing or other drugs have no effect on the overall availability of metoprolol to the systemic circulation but may have significant effects on the time to peak plasma concentration and peak concentration achieved after a single oral dose.

Elimination kinetics of labetalol in severe renal failure.

1 The pharmacokinetics of intravenously administered labetalol were studied in four patients with severe renal failure and in three normal subjects. 2 A new and sensitive method for the assay of plasma labetalol concentrations using high performance liquid chromatography is described. 3 Labetalol has a relatively large apparent volume of distribution (3.3-7.9 l/kg, two-compartment open model) and a relatively high plasma clearance (0.3-1.6 1 h-1 kg-1). 4 There were no significant differences between the patients with severe renal failure and the controls for any of the pharmacokinetic parameters measured. 5 In the presence of renal functional impairment, no modification of labetalol dosage is required. 6 In another study of 31 patients, glomerular filtration rate was measured at 3-month intervals for 3-18 months. In ten patients there was no change, in ten there was an improvement and in 11 there was deterioration, but in only three was this attributable to treatment. 7 In our experience with over 300 patients, we conclude that labetalol plus diuretic treatment is efficacious and safe in all grades of hypertension including those with all degrees of renal insufficiency.

Ibuprofen and diflunisal in rheumatoid arthritis: a double-blind comparative trial.

Both diflunisal (750 mg/day) and ibuprofen (1600 mg/day) were shown to be superior to placebo in the treatment of rheumatoid arthritis in a double-blind cross-over trial. Neither drug affected lymphocyte transformation to plant mitogens. Diflunisal scored better than ibuprofen at the dose levels chosen but the differences did not reach significance.

The antiemetic activity of tetrahydrocannabinol versus metoclopramide and thiethylperazine in patients undergoing cancer chemotherapy.

A double blind-cross-over randomised clinical trial has been conducted to compare the antiemetic effects of tetrahydrocannabinol, thiethylperazine and metoclopramide. There were no significant differences in the antiemetic effects of these drugs. The incidence of adverse reactions as recorded by both the staff and the patients was significantly higher in the tetrahydrocannabinol group than in either the metoclopramide or thiethylperazine groups. This trial has established that in the dosages used tetrahydrocannabinol given by mouth has an antiemetic effect of approximately the same order as thiethylperazine and metoclopramide. However, its adverse effects are sufficiently greater than those of the other agents to prevent is widespread usage for this purpose. Tetrahydrocannabinol taken by mouth is not recommended as a routine antiemetic agent in cancer chemotherapy.

Plasma and urine concentrations of acebutolol and its acetyl metabolite in patients with renal functional impairment.

This study was undertaken to examine the elimination of orally administered acebutolol and its major acetyl metabolite in four healthy controls and seven patients with varying degrees of renal functional impairment. Analysis of acebutolol and its metabolites was undertaken using a high performance liquid chromatographic method. Plasma concentrations of acebutolol and the acetyl metabolite were greater in patients with renal functional impairment than in controls. The elimination of acebutolol did not appear to be influenced by impaired renal function. However the elimination of the acetyl metabolite decreased as renal function diminished. Acebutolol has a major non-renal route of elimination, but the acetyl metabolite (also a beta-adrenoreceptor blocking drug) is primarily excreted by the kidney and may accumulate in renal failure.

Methanol monitoring. Comparison of urinary methanol concentration with formic acid excretion rate as a measure of occupational exposure.

Methods of monitoring occupational exposure to methanol were investigated in volunteer subjects who had ingested small amounts of methanol. It was confirmed that urinary methanol concentrations accurately reflected those in the blood. This relationship was maintained over a considerable range of concentrations in spite of large variations of urine flow. Concomitant ingestion of ethanolic beverages increased the urinary methanol concentration slightly. Urinary formic acid concentration was too variable to be of value but rate of urinary excretion of formic acid did reflect methanol uptake. The ratio of urinary formic acid to creatinine concentrations (F/C ratio) is a practical monitoring method. However, formic acid elimination rate is reduced by ingestion of ethanolic beverages. Urinary methanol concentration is favoured as a method of monitoring and a concentration of 10 microgram/ml measured at the end of the work shift is suggested as the level above which occupational exposure should be suspected and the appropriate action taken.

The aspirin-ibuprofen interaction in rheumatoid arthritis.

1 This was a double-blind crossover trial of ibuprofen and soluble aspirin against each drug alone and against placebo in patients with rheumatoid arthritis. Two dosage regimes were tested. 2 A weak clinical additive effect was demonstrated between soluble aspirin and ibuprofen in patients with rheumatoid arthritis using moderate (1600 mg ibuprofen and 3.6 g aspirin daily) but not low (800 mg ibuprofen and 2.4 g aspirin daily) dosages of both drugs. 3 A significant correlation between clinical efficacy and serum ibuprofen but not salicylate level was found in the single drug periods of the trial. 4 No consistent effect of ibuprofen administration on serum salicylate levels was found. 5 Concurrent salicylate administration produced significant lowering of serum ibuprofen levels without affecting elimination half-lives of the drug.

A comparative study of indomethacin and ibuprofen.

In a double blind trial with 20 patients ibuprofen 1600 mg daily and indomethacin 100 mg daily were shown to be of comparable efficacy in the short-term treatment of rheumatoid arthritis. Reported side effects were similar, but a slightly greater incidence of gastric irritation was noted with indomethacin necessitating withdrawal of one patient from the trial. The serum concentrations for indomethacin and ibuprofen were determined for four hours after the last dose. Peak concentrations of both drugs occurred within two hours. Five of the seven patients considered to have comparable serum concentrations of both drugs demonstrated a preference for indomethacin.

Serial hexachlorophene blood levels in the premature infant.

The concentration of hexachlorophene was determined in serial blood samples taken from seven premature infants washed with pHisoHex. Results indicated that after a single wash with 5ml of pHisoHex, blood concentrations reached a maximum of 0.75-1.20mug/ml two to four days after application. The results obtained in this study confirm that the dermal absorption of hexachlorophene is greater in premature than in full-term infants. Use of hexachlorophene for infants. Use of hexachlorophene for infants of birth weight less than 2kg has now been discontinued at Queen Mary Hospital and the amount of pHisoHex used in the initial toileting of infants with birth weight more than 2kg has been limited to a single application of 5ml.