Comparison of an age adjusted warfarin loading protocol with empirical dosing and Fennerty's protocol.

AIM: A warfarin loading protocol adjusting doses for age was compared to both Fennerty's protocol (Fenn) and empirical dosing (Emp). METHODS: Patients beginning warfarin were randomised to receive doses according to either the age adjusted (Age) protocol or Fenn. Data were retrospectively collected for patients who had begun warfarin in the previous six months to represent empirical dosing. The study was performed on inpatients being commenced on warfarin for the first time at two teaching hospitals. MAIN OUTCOME MEASURES: Endpoints were time to reach a stable, therapeutic International Normalised Ratio (INR) between 2-3, the number of patients experiencing an INR > or =4 in the first week and the number of patients who had a dose held in the first week. RESULTS: Thirty-five patients were assessed in the Age group, 28 in the Fenn group, and 123 patients for the Emp group. Patients using the Age protocol achieved a stable, therapeutic INR more rapidly than either the Fenn (p=0.003, log rank test) or Emp (p<0.001) group. The Age group had a lower proportion of patients experiencing an INR > or =4 in the first week (p<0.05) as well as a lower proportion having doses held in the first week (p<0.01). There were no differences between Emp and Fenn for any of the endpoints. CONCLUSION: Adjustment of warfarin loading doses for age exhibits clear superiority over the use of Fenn or Emp. This becomes increasingly important as the average age of patients being warfarinised increases, with the recognition that atrial fibrillation requires anticoagulation. Fenn consistently overdosed elderly patients, especially those aged 80 years and older.

High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response.

A commercially available 1.0 g intravenous (i.v.) dosage formulation of methylprednisolone, as the sodium hemisuccinate salt (Solu Medrol, Upjohn) was administered both parenterally and orally (pulse steroid therapy) on separate occasions, to eight elderly (mean 65 y) patients with active rheumatoid arthritis. The relative oral bioavailability of the sterol was 69.2%. Elimination of methylprednisolone was prolonged when given orally; the mean residence times were 7.23 h and 3.94 h for oral and i.v. administrations, respectively. Clinical response to pulse steroid therapy was no different with respect to route of administration. There were no significant differences in standard clinical and laboratory assessments of disease activity when the two therapies were compared. Oral administration of methylprednisolone in patients requiring high-dose pulse steroid therapy is convenient and avoids the discomfort and inconvenience associated with i.v. administration.

Standardised initial warfarin treatment: evaluation of initial treatment response and maintenance dose prediction by randomised trial, and risk factors for an excessive warfarin response.

We report a comparison of warfarin treatment outcomes in 172 inpatients in two general hospitals randomly assigned to commence warfarin therapy by one of two methods; the first where warfarin dosage was determined using a flexible dose induction protocol, and the other where dosage was prescribed empirically by resident medical staff. The mean INR for each treatment day, the mean time to reach a therapeutic level of INR, the mean maintenance dose and the mean time to reach maintenance dose were not significantly different between the protocol and empirical treatment groups. Although the mean observations of warfarin effect were similar between the two groups, there were more patients with excessive warfarin effect (INR greater than 4.0) during empirical treatment. In addition, age and identified complicating factors such as interfering drugs, heart failure or alcohol abuse were significant predictors of excessive warfarin effect, regardless of treatment group. The protocol dose administered on day 4 of treatment, which has been used as a determinant of maintenance dose, predicted maintenance dose to within 1 mg in 57/83 patients (69%, 95% confidence interval: 59-79%). We conclude that as a method for safely and effectively initiating warfarin therapy, this protocol at least matches the empirical prescribing skills of medical staff in a teaching hospital.

Formulation of 1-alpha,25-dihydroxycholecalciferol topical ointment for psoriasis treatment.

A means of accurate and rapid formulation of 1-Alpha,25-dihydroxycholecalciferol topical ointment is described. The accuracy of the formulation technique is within 95% of the theoretical ointment concentration (lug/gram of petrolatum base). Moreover, the stability of the formulated ointment is examined at room temperature (21 degrees C) and refrigerated (2 degrees C) over 40 days storage. When protected from light the loss of potency is 6% at 21 degrees C and negligible at 2 degrees C.

Prospective evaluation of a flexible protocol for starting treatment with warfarin and predicting its maintenance dose.

We have evaluated a flexible warfarin dose induction protocol by monitoring its performance in 100 elderly inpatients. The protocol (designed by Fennerty et al., has two aims: (a) to move the prothrombin time (PT) ratio smoothly and quickly into its therapeutic range, and (b) to predict the steady-state warfarin requirement from the PT ratio measured on the fourth treatment day. It proved simple to use and reasonably successful, since after four days, 67/100 patients had achieved a therapeutic level of PT ratio, nine exceeded the therapeutic range, and 24 remained sub-therapeutic, while none had bled due to excessive anticoagulation. Maintenance dose prediction was tested by comparing the predicted and observed maintenance doses in patients within the 'therapeutic range' of PT ratio after various median times of treatment. After ten days, the observed dose was within 1 mg of that predicted in 65/86 patients (76%). This proportion became 57/77 (74%) after 18 days, and 49/79 (62%) after 34 days.

Comparison of methylprednisolone (1 g i.v.) with prednisolone (1 g orally) in rheumatoid arthritis: a pharmacokinetic and clinical study.

Methylprednisolone pulse therapy is often used in patients with severe rheumatoid arthritis (RA). To compare clinical and pharmacokinetic variables of methylprednisolone and oral prednisolone in patients with RA, a controlled crossover study was carried out. Pharmacokinetic variables for methylprednisolone were Vd of 69.9 l, t1/2 of 2.96 h, total plasma clearance of 17.5 l/h. Pharmacokinetic variables for prednisolone were Vd of 47.5 l, t1/2 of 3.08 h and total plasma clearance of 11.3 l/h. During the elimination phase, a secondary rise in methylprednisolone concentration occurred which may be related to enterohepatic circulation. Clinical response to both prednisolone and methylprednisolone was short-lived with neither lasting more than 6 weeks.