Daily dosing

An ideal" drug must be safe and effective. The mavimum daily dose should not exceed 200-300 mg. Drugs should be well absorbed orally and bioavailablc. Metabolic stability ensures a reasonable long half-life. Further on, a drug should be non-... 

Relative potency alone does not determine dmg selection because maximal effectiveness is similar for all agents. A single daily dose of any sulfonylurea, except tolbutamide, is sometimes adequate to control blood glucose in NIDDM patients. 

A recent study recommended that the current RDA be increased from 60 mg/d to 200 mg. The researchers indicated, however, that vitamin C daily doses above 400 mg have no value (163). 

Dietary deficiency in the absence of absorption defects can be effectively reversed with oral supplementation of 1 p.m of vitamin B 2 daily. If deficiency is related to a defect in vitamin absorption, daily doses of 1 pg adininistered subcutaneously or intramuscularly are effective (33). However, a single intramuscular dose of 100 pg of cobalamin once per month is adequate in patients with chronic gastric or ileal damage. Larger doses are generally rapidly cleared from the plasma into the urine and are not effective unless the patient demonstrates poor vitamin retention. 

At the tested daily dose of 50 mg, fluconazole appears to be slightly less active against dermatophytes. The substance is used mainly to treat vaginal candidosis (a single capsule of 150 mg) and oral and esophageal candidosis (50 mg od for 14 d). In a number of countries, ie, England, the maximal period of treatment is 14 d. 

The antiviral mechanism of action of acyclovir has been reviewed (72). Acyclovir is converted to the monophosphate in herpes vims-infected cells (but only to a limited extent in uninfected cells) by viral-induced thymidine kinase. It is then further phosphorylated by host cell guanosine monophosphate (GMP) kinase to acyclovir diphosphate [66341 -17-1], which in turn is phosphorylated to the triphosphate by unidentified cellular en2ymes. Acyclovir triphosphate [66341 -18-2] inhibits HSV-1 viral DNA polymerase but not cellular DNA polymerase. As a result, acyclovir is 300 to 3000 times more toxic to herpes vimses in an HSV-infected cell than to the cell itself. Studies have shown that a once-daily dose of acyclovir is effective in prevention of recurrent HSV-2 genital herpes (1). HCMV, on the other hand, is relatively uninhibited by acyclovir. 

Carcinogen Potency Factor (CPF) A CPF is the slope of the dose-response cun e at very low exposures. The dimensions of a CPF, are expressed as the iin erse of daily dose (mg/kg-day)". ... 

Note The RSD is an estimate of tlie average daily dose of a careinogen tliat... 

Perhaps one of the most exciting new applications stems from the discovery in 1949 that small daily doses (l-2g) of LI2C03 taken orally provide an effective treatment for manic-depressive psychoses. The mode of action is not well understood but there appear to be no undesirable side effects. The dosage maintains the level of Li in the blood at about I mmol l and its action may be related to the influence of Li on the Na/K balance and (or) the Mg/Ca balance since Li is related chemically to both pairs of elements. 

Daily doses of 3-8 mg (6-8 times 0.5-1.0 mg) are used for the treatment of acute gouty arthritis. For prophylaxis, daily doses of 0.5-1.5 mg are used, but the use of colchicine for prophylaxis is controversial. 

The daily dose of allopurinol is 300-600 mg. In combination with benzbromarone, the daily allopurinol dose is reduced to 100 mg. In general, allopurinol is well tolerated. The incidence of side effects is 2-3%. Exanthems, pruritus, gastrointestinal problems, and dty mouth have been observed. In rare cases, hair loss, fever, leukopenia, toxic epidermolysis (Lyell syndrome), and hqDatic dysfunction have been reported. Allopurinol inhibits the metabolic inactivation of the cytostatic dtugs azathioprine and 6-mercaptopurine. Accordingly, the administered doses of azathioprine and 6-mercaptopurine must be reduced if allopurinol is given simultaneously. 

The daily dose of benzbromarone is 50-200 mg. In combination with allopurinol, the benzbromarone dose is reduced to 20 mg. Benzbromarone is well tolerated. Rare side effects are headaches, gastrointestinal problems, and exanthems. 

The daily dose ofprobenecid is 0.5-3.0 g. Probenecid is well tolerated, and there are few serious side effects. In... 

The daily dose of sulfinpyrazone is 200-400 mg. The side effects of sulfinpyrazone are comparable with those of probenecid. A potential therapeutic advantage of sulfinpyrazone in patients with coronary heart disease and thromboembolic diseases is its inhibitory effect on platelet aggregation. 

Initial daily doses of 10-40 and 100-600 mg are recommended in clinical practice for MMI and PTU, respectively [1, 2]. Several studies have shown that treatment of hyperthyroidism with single daily doses of 10-40 mg of MMI is effective in the induction of euthyroidism in 80-90% of patients within 6 weeks [2]. The aim of the further antithyroid therapy is to maintain euthyroidism with the lowest necessary diug dose. Intrathyroidal diug accumulation is one cause for the efficiency of a single daily dose regimen. Moreover, a once daily dose yields better patients compliance. Single daily doses of PTU have been shown to be less effective in achieving euthyroidism than administration of three divided doses a day. If a once daily... 

Anastrazole is a nonsteroidal, type H, aromatase inhibitor that is 200 times more potent than aminoglutethimide. It is eliminated primarily via hqDatic metabolism, has a terminal half life of 50 h with steady state concentrations achieved approximately 10 days with once daily dosing regimens. It is administered orally at a dose of 1 mg/day that achieves near maximal aromatase inhibition and hence estrogen suppression in breast cancer patients. No effect on adrenal steroidogenesis has been observed at up to ten times the daily recommended dose. When used in the metastatic setting, anastrozole has been shown... 

Intestinal absorption of digoxin is less complete compared to digitoxin. In order to improve absorption, acetylated- and methylated-digoxin derivates were developed. Digitoxin is metabolised in hepatic microsomal enzymes and can be cleared independently from renal function. The therapeutical serum level of digoxin is 0.5-2.0 ng/ml and 10-35 ng/ml of digitoxin. Steady state plateau of therapeutic plasma concentrations is reached after 4-5 half-life-times using standard daily doses [5]. 

Oxicams, e.g. piroxicam, tenoxicam, meloxicam and lornoxicam are non-specific inhibitors of COX. Like diclofenac, meloxicam inhibits COX-2 ten times more potently than COX-1. This property can be exploited clinically with doses up to 7.5 mg per day, but at higher doses COX-1-inhibition becomes clinically relevant. Since the dose of meloxicam commonly used is 15 mg daily, this agent cannot be regarded as a COX-2-selective NS AID and considerable caution needs to be exercised when making comparisons between the actions of meloxicam and those of other conventional NSAIDs. The average daily dose in anti-rheumatic therapy is 20 mg for piroxicam and tenoxicam, 7.5-15 mg for meloxicam and 12-16 mg for lornoxicam. Oxicams have long elimination half-lives (lornoxicam 3-5 h, meloxicam - 20 h, piroxicam 40 h and tenoxicam 70 h). 

According to Lazarev (Ref 27) a single lethal dose for a cat is 0.5g/kg of its weight. A daily dose of 0.05—0.2g/kg causes death after 9 days Saladini (Ref 15a) pointed out that small doses of PA cause no ill-effects in man... 

Status eptIepticus may result from abrupt discontinuation of the drug, even when the anticonvulsant is bang administered in smalt daily doses. 

---