Lowered plasma concentrations

Fosfomycin is contraindicated in patients with a hypersensitivity to the drug. Fosfomycin is used cautiously during pregnancy (Pregnancy Category B) and lactation. There is a lowered plasma concentration and urinary tract excretion when fosfomycin is administered with metoclopramide... 

Chinese depressed patients appeared to require lower dosages, with consequently lower plasma concentrations of sertraline compared to Caucasian patients to achieve clinical efficacy (Ng et al, 2006). Again, this finding has supported the fact that Asian patients, especially Chinese, need lower doses of antidepressant drugs than their Western counterparts. 

CYP 450 Lopinavir/ritonavir is metabolized by CYP3A. Drugs that induce CYP3A activity would be expected to increase the clearance of lopinavir, resulting in lowered plasma concentrations of lopinavir. Although not noted with concurrent ketoconazole, coadministration of lopinavir/ritonavir and other drugs that inhibit CYP3A may increase lopinavir plasma concentrations. 

Quinidine s effect on the electrical properties of a particular cardiac tissue depends on the extent of parasympathetic innervation, the level of parasympathetic tone, and the dose. The anticholinergic actions of quinidine predominate at lower plasma concentrations. Later, when steady-state therapeutic plasma concentrations have been achieved, the drug s direct electrophysiological actions predominate. The direct and indirect electrophysiological actions are summarized in Table 16.2. 

Nevirapine induces and is metabolized by CYP3A4 therefore, coadministration of drugs that induce or are metabolized by this isoenzyme may result in interactions. Nevirapine may decrease the effectiveness of ethinyl estradiol-based contraceptives and can lower plasma concentrations of methadone. Nevirapine should not be administered with ketoconazole, rifampin, or rifabutin. 

Following oral treatment, suxibuzone is slowly absorbed from the gastrointestinal tract, but is very rapidly distributed in the body. In all species, suxibuzone was rapidly metabolized to phenylbutazone, which subsequently was metabolized to oxyphenbutazone and -hydroxyphenylbutazone. Animals treated with suxibuzone exhibited lower plasma concentrations of the parent drug than the phenylbutazone metabolite. Available data on phenylbutazone, the principal suxibuzone metabolite, indicated that phenylbutazone has carcinogenic potential for animals. 

St. John s wart, rifampin, efavirenz, nevirapine and amprenavir will lower plasma concentrations of lopinavir due to their effect on cytochrome P-450 enzyme CYP3A4. Lopinavir increases plasma concentrations of ergot derivatives, triazolam, midazolam, and propafenone and should not be given together. 

The effect of continuously administered low-dose 17-beta-estradiol (E2) + norethisterone acetate (NETA) on coagulation and fibrinolytic factors has been studied in 120 menopausal women, using two dosage variations (1 mg of E2 with 0.25 mg or 0.5 mg of NETA) compared with placebo over a year (53). In either dose, the combination significantly lowered plasma concentrations of factor VII, fibrinogen, antithrombin, and plasminogen activator inhibitor-1 (PAI-1) compared with placebo. These changes appear favorable, since they may lead to increased fibrinolytic activity and could reduce the risk of coronary heart disease. However, antithrombin activity was also reduced, which may increase the risk of venous thromboembolism. 

Cyclosporin A is slowly but extensively metabolized. The biotransformation pathway and the pattern of the generated metabolites are similar in humans and animals. Approximately 17 single metabolites have been detected so far, all of which are present in considerably lower plasma concentration than cyclosporin A itself [46]. Eleven ether-extractable compounds have been isolated from urine of dog and man and from rat bile and faeces using preparative HPLC and thin-layer chromatography [43]. Structural assignments for these... 

It thus seems unlikely that intakes of vitamin Bg above amounts that are adequate to prevent metabolic signs of deficiency will be beneficial in lowering plasma concentrations of homocysteine (ffomocysteine Lowering Trialists Collaboration, 1998). 

At tbe time that the U. K. and European Union reference intakes of folate shown in Table 10.3 were being discussed, the results of intervention trials for the prevention of neural tube defects (Section 10.9.4) were only just becoming available. At that time, there was no information concerning the effects of folate status onhyperhomocysteinemia (Section 10.3.4.2). TheU.S./Canadianreport (Institute of Medicine, 1998) notes specifically that protective effects with respect to neural tube defects were not considered relevant to the determination of the Dietary Reference Intake of folate, and there was insufficient evidence to associate higher intakes of folate (and lower plasma concentrations of homocysteine) with reduced risk of cardiovascular disease. 

It has been suggested that preterm infants may require a dietary source of preformed taurine breast mifk initially contains a high concentration (about 300 /xmol per L), and breast-fed infants maintain a higher plasma concentration of taurine than those fed on formula without added taurine (Chesney et al., 1998). Although mUk from vegan mothers has a low concentration of taurine, and their infants have lower plasma concentrations and urinary excretion of taurine than the infants of omnivore mothers, there is no evidence that (full-term) infants of vegan mothers show any signs of taurine deficiency. 

Oral contraceptives may increase clearance and lower plasma concentrations of lorazepam... 

Dose is 250 mg 6-hourly or twice this in serious infection and four times this for Legionnaires disease. The ethylsuccinate and stearate esters of erythromycin produce lower plasma concentrations of the active drug than does the same dose of the estolate. 

An example of the results of a steady-state study, with dosing every 6 hr, is illustrated in Fig. 3. The pharmacokinetic data employed to generate the results shown in Fig. 3 were identical to those used for Fig. 2. The results demonstrate the influence of the rate and extent of absorption on the steady-state plasma concentrations. The lower plasma concentrations shown for product C reflect the lower extent of absorption for this product. Products A and B have the same extent of absorption, but differ in rate of absorption. Product A is more rapidly absorbed than product B, and thus there is a greater fluctuation between the maximum and minimum concentrations at steady state. 

After subcutaneous administration the systemic availability of epoetin is not complete (20%) and lower plasma concentrations are observed than after intravenous administration. However, the apparent half-life of epoetin is prolonged after subcutaneous injection, and this allows the use of lower doses to obtain an equivalent hemoglobin concentration (38). Subcutaneous injections are more effective when given thrice weekly rather than once weekly (38). 

Most patients treated for neurocysticercosis with praziquantel develop an early cerebrospinal fluid reaction a similar late reaction, some 2 weeks after treatment has finished, has also been described (16). In both cases clinical signs and sjmptoms can include papilledema, headache, nausea, vomiting, neck stiffness, and even focal seizures. Glucocorticoids can usually prevent or relieve both the early and late reactions, but they can also reduce efficacy by lowering plasma concentrations of the drug by some 50% (17). 

It has been suggested that there may be some benefit of using tryptophan in selected patients, particularly those with psychomotor retardation (3). Unfortunately, most of these reports have appeared as letters to the editors of journals (4-6) or as preliminary communications (7). In addition to the possible absence of any consistent effect, there are many plausible reasons to explain the variabihty in response. Tryptophan has been given in both the racemic and monomeric (levorotatory) forms, both alone and together with a number of substances intended to increase the synthesis or availability of serotonin, including monoamine oxidase (MAO) inhibitors (8), potassium or carbohydrate supplements (9), and co-enzymes such as pyridoxine or ascorbic acid (10). It has also been suggested that tryptophan plasma concentrations have a therapeutic window (4), and that repeated administration induces hepatic tryptophan pyrrolase, resulting in lowered plasma concentrations and loss of therapeutic effect after 2 weeks of treatment (8). Attempts have been made to amehorate this problem by coadministration of nicotinamide (4). 

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