Pharmacokinetics and bioavailability of flucloxacillin in elderly hospitalized patients.

The pharmacokinetics and oral bioavailability of flucloxacillin were studied in five female and two male patients (age 68-87 yr) who had been hospitalized for orthopedic surgeries. A single dose of intravenous or oral flucloxacillin sodium (500 mg) was administered in random order on different occasions separated by at least 2 days. Blood and urine samples were taken up to 24 hours after drug administration and levels of flucloxacillin and 5-hydroxymethylflucloxacillin (5-HMF), a major metabolite, were measured by high-performance liquid chromatography. Flucloxacillin elimination, but not oral absorption, was reduced in the elderly, compared with data from young healthy subjects reported elsewhere. Total clearance, renal clearance, and volume of distribution were 0.083 +/- 0.013 L/kg/hr, 0.038 +/- 0.01 L/kg/hr, and 0.184 +/- 0.034 L/kg, respectively. Regression of flucloxacillin renal clearance (Clr) on estimated creatine clearance (CLcr) gave the relationship: Clr = 0.755 (CLcr) + 10.6 (r = 0.91; P = 0.004). Terminal half-lives for flucloxacillin and 5-HMF were 2.21 +/- 0.51 hr and 3.0 +/- 0.75 hr, respectively after intravenous administration. Flucloxacillin was absorbed rapidly after oral administration with a mean absorption time of 0.95 +/- 0.34 hr, and time to reach peak concentration of 1.20 +/- 0.29 hr. The absolute bioavailability of flucloxacillin from capsules was 54.4 +/- 18.8%.

A retrospective study of risk factors of akathisia in terminally ill patients.

Akathisia is a distressing disorder that manifests as a state of restlessness and motor agitation. We aim to highlight the problem of akathisia to the palliative care physician by identifying and quantifying risk factors in the terminally ill. A retrospective case-control study was utilized to investigate risk factors for akathisia. Medical records of cases (N = 100) and controls (N = 365) archived in a computerized database were downloaded and risk factors determined using conditional logistic regression analyses. Exposure to pharmacologically similar drugs, such as haloperidol [odds ratio (OR), 18.4; 95% confidence interval (CI), 8.2-41.4], prochlorperazine (OR, 8.1; 95% CI, 3.0-21.8), and promethazine (OR, 3.3; 95% CI, 1.3-8.0), conferred an increased risk. Other significant variables were exposure to morphine (OR, 5.3; 95% CI, 1.9-14.2), sodium valproate (OR, 2.5; 95% CI, 1.0-6.4), and sodium bicarbonate/tartrate (Ural) (OR, 4.2; 95% CI, 1.2-15.3). Highlighting factors that predispose patients to akathisia emphasizes that this syndrome should not be forgotten when treating the terminally ill. It is recommended that those drugs identified should be judicially used and carefully monitored.

Individual theophylline dosing based on bioelectrical impedance analysis.

The role of bioelectrical impedance (BI) analysis in determining slow-release theophylline dosage was evaluated in fifteen healthy subjects given a standard 200 mg dose. Reactance and l/resistance were identified as the most significant predictors of pre-dose, steady-state theophylline concentrations (Css,pre). Compared with doses based on body weight (8.8 mg kg-1 day-1), theophylline doses determined by BI analysis (9.6 +/- 2.4 mg kg-1 day-1) resulted in less biased (mean prediction error = 0.6 vs 1.4) though slightly less precise (mean squared error = 7.1 vs 6.3) Css,pre values. These differences were statistically insignificant (P > 0.05).

Implications of AIDS for teachers of medicine to dental students.

A plea is made for a significant input on AIDS to the dental undergraduate curriculum by medical teachers. The suspicion is that in some schools the teaching of medicine to dental students is not treated seriously. Figures are quoted depicting the worldwide spread of AIDS. The risk of dentists acquiring HIV in the health care setting is discussed. Mention is made of infection control in the dental environment. The objectives are given of a medical curriculum for dental students. Some of the oral manifestations of AIDS are named. Symptoms and signs (which a dentist should be able to recognize) are given for pulmonary, neurological, gastrointestinal or neoplastic complications that may be found in HIV infection. The role of the dentist is stressed in continuing surveillance of patients with HIV infection.

HIV and the dental undergraduate.

Reasons are offered as to why it is imperative that the dental undergraduate is familiar with all aspects of AIDS. The epidemiology of the disease is discussed, as are methods of transmission of the virus. A classification is given of the clinical presentation of HIV infection. The classification is based on the system put forward by the Centers for Disease Control, Atlanta. A brief résumé is given of laboratory diagnosis in HIV infection, and of the risk of health care workers contracting the disease. The precautions recommended for use in dentistry as proposed by the Centers for Disease Control are quoted in full. Finally mention is made of the treatment and control of AIDS.

The pharmacokinetics of amiloride-hydrochlorothiazide combination in the young and elderly.

The pharmacokinetics of amiloride and hydrochlorothiazide were studied in 12 healthy young volunteers following a single dose of a fixed combination of amiloride and hydrochlorothiazide and in 11 elderly hypertensive patients at steady-state. Following modelling of the single dose data, simulated steady-state plasma concentrations for the 2 drugs were generated to examine the effect of age and/or hypertension on pharmacokinetics. The apparent systemic plasma clearance for both amiloride and hydrochlorothiazide was significantly reduced in the elderly when compared to the young (from 753 to 325 ml.min-1, amiloride; and from 418 to 157 ml.min-1, hydrochlorothiazide). The plasma concentrations at steady state for both drugs were greatly increased in the elderly patients (Amiloride: from 7 to 25 ng.ml-1, Css,max; from 2 to 8 ng.ml-1, Css,min; and from 4 to 14 ng.ml-1, Cav; Hydrochlorothiazide: from 184 to 651 ng.ml-1, Css,max; from 31 to 121 ng.ml-1, Css,min; and from 89 to 273 ng.ml-1, Cav). The decreased clearance of the diuretics in the elderly was believed due to deterioration of renal function, and there was a significant correlation between the plasma clearance of hydrochlorothiazide and creatinine clearance in both age groups (r = 0.62, young; r = 0.72, elderly). As a result of the pharmacokinetic findings caution may be indicated in the clinical dosage of the diuretics particularly when in fixed dose combination.

Comparison of plasma levels of canrenone and metabolites after base hydrolysis in young and elderly subjects following single and multiple doses of spironolactone.

Plasma levels of canrenone and 'total metabolites' after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and 'total metabolites' were higher in the young than in the elderly group, and significant differences were found between the two age groups in the AUC for both canrenone and 'total metabolites'. However, these differences between the two age groups diminished after multiple dosing on Day 8, and the steady state pre-dose plasma levels of canrenone and 'total metabolites' were significantly higher in the elderly subjects. The accumulation ratios of canrenone and 'total metabolites' were significantly higher in the elderly than in the young subjects. Both canrenone and canrenoic acid were extensively bound to plasma protein, but no differences were found between the two age groups in protein binding. Observed differences in plasma levels after single and multiple dosing between young and old subjects may be consequences of many factors such as a proportionate shift in metabolism with age; impaired oral absorption of the parent compound; and/or altered volume of distribution of the drug.

Plasma protein binding of phenytoin in the aged: in vivo studies.

1 The relation between plasma water phenytoin content and whole plasma phenytoin content in vivo was studied in 22 elderly patients (age range 62 to 87 years) and in 22 young patients (age range 18 to 33 years), all of whom were taking the drug for epilepsy. 2 The percentage of the drug existing unbound in plasma was slightly, but statistically significantly, higher in the elderly (12.8 +/- 1.8%) than in the young (11.1 +/- 2.5%). Reduced plasma albumin levels in the elderly (33.0 +/- 2.0 gl-1) as compared with the young (45.3 +/- 3.5 gl-1) probably contributed to the reduced protein binding in the older subjects.

The care of diabetes mellitus at a community health centre.

Diabetes mellitus is a chronic disease with a high prevalence of about 2.0 per cent in the australian community. Although hospital diabetic clinics play an important role in the management of diabetic patients, the majority are managed by their local doctor. In this article the possible role of a health centre in the care of diabetics is outlined.