Liver loading dose

In patients with a history of AED use, a baseline serum concentration may be useful to determine if the drug concentration is below the desired range and if a loading dose is needed. Albumin levels, renal function tests, and liver function tests can also be helpful when assessing antiepileptic therapy. 

The ability of the liver to act as a depot for vitamin Bi2 (B28, G13) enables us to use this vitamin as an index of proper hepatic function. Hepatic disorders lead to an increased Bi2-binding in the serum (J5, R3), suggesting that the blood assumes a greater role in the conservation of B12. We have reported that patients with liver disease excreted invariably less than 10 fig of Bi2> 8 hours after a 50-[ig intramuscular load dose of the vitamin. In contrast, normal subjects excreted 24-40 pg, i.e., 50-80% of the vitamin in the same test (B14). These results were correlated with various chemical determinations indicative of hepatic disorders (Bl). In Table 16 the clinical diagnosis and the various liver-... 

Correlation of Vitamin B12 Excretion and Liver Function Tests 8 Hours After a 60 ig Load Dose... 

PO loading dose 400 mg tid x 15-30 days, then 200-400 mg qd (5-10 mg/l ) pneurrwnitis when dose >400 mg/d elevation of digoxin level, prolongation of prothrombin time (70-100%) with warfarin pultrwnary fibrosis, hepatitis, ocular opacities proarrhythmic monitor thyroid and liver function... 

Sparfloxacin - Sparfloxacin is well absorbed following oral administration. Steady-state concentration was achieved on the first day by giving a loading dose that was double the daily dose. Oral absorption of sparfloxacin is unaffected by administration with milk or food, including high-fat meals. Sparfloxacin distributed well into the body. It penetrates well into body fluids and tissues. Sparfloxacin is metabolized by the liver. It is excreted in the feces (50%) and urine (50%). 

Evaluate liver function tests at the start of and during the course of voriconazole therapy. Monitor patients who develop abnormal liver function tests during voriconazole therapy for the development of more severe hepatic injury. Discontinuation of voriconazole must be considered if clinical signs and symptoms consistent with liver disease develop that may be attributable to voriconazole. Hepatic function impairment It is recommended that the standard loading dose regimens be used but that the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis (Child-Pugh class A and B) receiving voriconazole. 

Dosage in liver impairment 100 mg q6h (200 mg q 12h with extended-release). Dosage in cardiomyopathy, cardiac decompensation No loading dose 100 mg q6-8h with gradual dosage adjustments. 

In patients with heart failure, lidocaine s volume of distribution and total body clearance may both be decreased. Thus, both loading and maintenance doses should be decreased. Since these effects counterbalance each other, the half-life may not be increased as much as predicted from clearance changes alone. In patients with liver disease, plasma clearance is markedly reduced and the volume of distribution is often increased the elimination half-life in such cases may be increased threefold or more. In liver disease, the maintenance dose should be decreased, but usual loading doses can be given. Elimination half-life determines the time to steady state. Thus, although steady-state concentrations may be achieved in 8-10 hours in normal patients and patients with heart failure, 24-36 hours may be required in those with liver disease. Drugs that decrease liver blood flow (eg, propranolol, cimetidine) reduce lidocaine clearance and so increase the risk of toxicity unless infusion rates are decreased. With infusions lasting more than 24 hours, clearance falls and plasma concentrations rise. Renal disease has no major effect on lidocaine disposition. 

Clarithromycin is metabolized in the liver. The major metabolite is 14-hydroxyclarithromycin, which also has antibacterial activity. A portion of active drug and this major metabolite is eliminated in the urine, and dosage reduction (eg, a 500-mg loading dose, then 250 mg once or twice daily) is recommended for patients with creatinine clearances less than 30 mL/min. Clarithromycin has drug interactions similar to those described for erythromycin. 

Quinine is derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. The alkaloid quinine was purified from the bark in 1820, and it has been used in the treatment and prevention of malaria since that time. Quinidine, the dextrorotatory stereoisomer of quinine, is at least as effective as parenteral quinine in the treatment of severe falciparum malaria. After oral administration, quinine is rapidly absorbed, reaches peak plasma levels in 1-3 hours, and is widely distributed in body tissues. The use of a loading dose in severe malaria allows the achievement of peak levels within a few hours. The pharmacokinetics of quinine varies among populations. Individuals with malaria develop higher plasma levels of the drug than healthy controls, but toxicity is not increased, apparently because of increased protein binding. The half-life of quinine also is longer in those with severe malaria (18 hours) than in healthy controls (11 hours). Quinidine has a shorter half-life than quinine, mostly as a result of decreased protein binding. Quinine is primarily metabolized in the liver and excreted in the urine. 

In a pilot study after coronary angioplasty in 22 patients, sirolimus was given orally in a loading dose of 6 mg followed by 2 mg/day over 4 weeks. Sirolimus was withdrawn after an average of 15 days in 11 patients because of adverse effects, including hypertriglyceridemia (n — 3), leukopenia (n = 3), raised liver function tests, stomatitis, acne, flu-like symptoms, and physician preference (n — 1 each). The rate of coronary restenosis was 87%. Sirolimus did not benefit patients with recalcitrant stenosis and adverse effects were frequent (1069). 

The safety and tolerability of once-daily oral metrifonate has been evaluated in patients with probable mild to moderate Alzheimer s disease in a randomized, doubleblind, placebo-controlled, parallel-group study (9). Metrifonate was given to 29 patients as a loading dose (2.5 mg/kg) for 2 weeks, followed by maintenance dose (1 mg/kg) for 4 weeks 10 patients received placebo. The proportion of patients who had at least one adverse event was comparable in the two groups metrifonate 76%, placebo 80%. Selected adverse events, defined as those for which the incidence in the metrifonate and placebo group differed by at least 10%, were diarrhea, nausea, leg cramps, and accidental injury. The adverse events were predominantly mild and transient. Those who took metrifonate had a significantly lower heart rate. Metrifonate had no clinically important effect on laboratory tests, such as liver function tests, and did not affect exercise tolerance or pulmonary function. 

Kynurenine Hydroxylase Kynurenine hydroxylase is an FAD-dependent mixed-function oxidase of the outer mitochondrial membrane, which uses NADPH as the reductant. The activity of kynurenine hydroxylase in the liver of riboflavin-deficient rats is only 30% to 50% of that in control animals, and deficient rats excrete abnormally large amounts of kynurenic and anthranilic acids after the administration of a loading dose of tryptophan, and, correspondingly lower amounts of quinolinate and niacin metabolites. Riboflavin deficiency may thus be a contributory factor in the etiology of pellagra when intakes of tryptophan and niacin are marginal (Section 8.5.1). 

It is not known to what extent taurine may be a dietary essential for human beings. There is little cysteine sulfinic acid decarboxylase activity in the human liver and, like the cat, loading doses of methionine and cysteine do not result in any significant increase in plasma taurine. This may be because cysteine sulfinic acid can also undergo transamination to /3-sulfhydryl pyruvate, which then loses sulfur dioxide nonenzymically to form pyruvate, thus regulating the amount of taurine that is formed from cysteine. There is no evidence of the development of any taurine deficiency disease under normal conditions. 

Pharmacokinetics. Amiodarone is effective given orally its enormous apparent distribution volume (701/kg) indicates that little remains in the blood. It is stored in fat and many other tissues and the t) of 54 days after multiple dosing signifies slow release from these sites (and slow accumulation to steady state means that a loading dose is necessary, see Table 24.1). The drug is metabolised in the liver and eliminated through the biliary and intestinal tracts. 

In 3325 patients who took leflunomide, the rate of drug withdrawal was 42% within 33 months after approval by the US Food and Drugs Administration, and was more likely in patients who received a loading dose. The most common causes of discontinuation were inefficacy (30%), gastrointestinal symptoms (29%), non-adherence to therapy or loss to follow-up (14%), and raised liver enzymes (5%) (50). 

An example of this approach can be obtained by continuing the theophylline patient case from the section on drug dosing in liver disease. In this example, a 55-year-old, 70-kg man with liver cirrhosis was prescribed a loading dose of theophylline 350 mg intravenously over 20 to 30 minutes, followed by a maintenance dose of 15 mg/h of theophylline as a continuous infusion. The infusion began at 9 A.M., blood samples were obtained at 10 A.M. and 4 P.M., and the clinical laboratory reported the theophylline serum concentrations as 10.9 and 12.3 mg/L, respectively. The patient s theophylline clearance and revised continuous infusion to maintain a Css of 15 mg/L can be computed as follows (patient s Vo estimated at 0.5 L/kg) ... 

Studies of leflunomide in kidney and liver transplant recipients utilized a loading dose of 200 mg daily for 7 days, followed by a maintenance dose of 40 to 60 mg daily. The target concentration appears to be 50 to 80 mcg/mL, which also allows for lower doses of steroids and CIs. A small open-label pilot study reported potential benefit with leflunomide in reversing chronic renal allograft dysfunction. ... 

Liver dioxygenase has a high Km and is probably active only when levels of tryptophan are high, such as after a meal or a loading dose, but this enzyme is probably not very effective when blood levels of tryptophan are normal. 

Treatment was initiated for paracetamol (acetaminophen) overdose. N-acetyl-L-cysteine is administered orally as follows. A loading dose of 140 mg/kg followed by 17 doses of 70 mg/kg every four hours. The patient was transferred to the intensive care unit. Her liver function tests and serum electrolytes returned to normal values during the next eight days (Table 2). The patient s... 

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