Mean plasma

Imidazole antimycotics, ketoconazole, clotrimazole, and miconazole are potent inhibitors of various cytochrome P450-isoenzymes that also affect the metabolism of retinoids. They were fust shown to inhibit the metabolism of RA in F9 embryonal carcinoma cells. When tested in vitm liarazole, a potent CYP-inhibitor, suppressed neoplastic transformation and upregulated gap junctional communication in murine and human fibroblasts, which appeared to be due to the presence of retinoids in the serum component of the cell culture medium. Furthermore, liarazole magnified the cancer chemopreventive activity of RA and (3-carotene in these experiments by inhibiting RA-catabolism as demonstrated by absence of a decrease in RA-levels in the culture medium in the presence of liarazole over 48 h, whereas without liarazole 99% of RA was catabolized. In vivo, treatment with liarazole and ketoconazole reduced the accelerated catabolism of retinoids and increased the mean plasma all-irans-RA-concentration in patients with acute promyelocytic leukemia and other cancels. 

Mean plasma, erythroc54e, and brain cholinesterase activities were significantly reduced by 67-88%, 9-20%, and 76-79%, respectively, in rats of both sexes following 2-year exposures to 2.5 mg/kg/day methyl parathion (Suba 1984). This effect did not occur in rats exposed to either 0.025 or 0.25 mg/kg/day methyl parathion. 

Mean Plasma Carotenoid Levels (timol/l) in EPIC Study Subjects from... 

Fig. 6 Mean plasma levels of atenolol in six male volunteers after a 100-mg tablet alone (O), with 25 mg of metoclopra-mide ( ), or with 30mg of propantheline ( ). (From Ref. 11.). 

Fig. 14 Mean plasma phenacetin concentrations in six adult volunteers following administration of 1.5-g doses (in aqueous suspensions containing 200 mg of phenacetin per milliliter). (From Ref. 18.).

Fig. 15 Mean plasma levels for groups of ten human subjects receiving single 0.5-g doses (as two 250-mg capsules) of chloramphenicol preparations A, B, C, or D. Vertical lines represent one standard error on either side of the mean. (From Ref. 19.).

Fig. 20 Mean plasma concentrations of unchanged drug from 12 subjects following administration of four different preparations of p-aminosalicylic acid (PAS). Data were corrected to 70 kg of body weight and to a dose equivalent of 4 g of free acid. (From Ref. 24.).

Fig. 22.3. Mean plasma concentration-time profiles of aciclovir following administration of 1000 mg oral valaciclovir or a 350-mg intravenous infusion of aciclovir over a 1-h period.

Figure 2 Mean plasma (Cp), CSF (CCSF), and brain (Cb) compound concentration-time profiles (graph) and matrix-specific neuropharmacokinetic parameters (table) of a compound in rats following subcutaneous administration [42]. Abbreviations Cmax, maximal compound concentration Tmax, time of Cmax tV2, compound half-life.

The answer is b. (Hardman, p 23.) When a drug is administered in multiple doses and each dose is given prior to the complete elimination of the previous dose, the mean plasma concentration (C) of the drug during each dose interval rises as shown in the following figure ... 

BPH—benign prostatic hypertrophy BPM—breaths per minute beats per minute BUN—blood urea nitrogen C—mean plasma concentration Cmi]X—maximum plasma concentration Cmm—minimum plasma concentration C albicans—Candida albicans C. bofulinum—Clostridium frotu/irtum C. difficile—Clostridium difficile C. jejuni—Campylobacter jejuni C. neoformans—Cryptococcus neoformans Ca—calcium... 

Venous blood levels of cyanide reached a steady state (mean value, 200 g/100 mL) within 10 min of exposure of cynomolgus monkeys at 100-156 ppm (Purser et al. 1984). The blood level stayed constant during the remainder of the 30-min exposure, during which time the animals lost consciousness the blood level remained the same for 1 h after exposure, even though the monkeys recovered consciousness within 10 min. The mean concentration of whole blood cyanide in rabbits that died following inhalation exposure was 170 pg/100 mL the mean plasma concentration was 48 figHOO mL (Ballantyne 1983). 

Also, the notation (p, d) means plasma, dynamic and for we have of course to take the equilibrium distribution... 

The elimination constant for a chemical in plasma. Typically calculated using the formula Kel = — ln[10] x b where b is the slope of the linear regression line of the log of the mean plasma concentrations vs. time from the tmsx to 24 hours. 

Figure 19 Mean plasma concentrations following the administration of felodipine suspension to Labradors. Median particle size 125 pm in = 6) dose 10 mg, in either 0.9% saline (NS) or 5% glucose (Glc.) solution. Source From Ref. 30.

Limited data are available on the pharmacokinetics of arecoline. Intravenously administered arecoline in subjects with Alzheimer s disease shows variation in the optimal dose (between 4 and 16 mg/day) due to differing plasma kinetics (Asthana et al. 1996). The mean plasma half-lives for these doses were 0.95 0.54 and 9.3 4.5 minutes, respectively. However, the mean plasma concentrations that optimized cognitive effects were 0.31 0.14 ng/ml. Drug clearance was 13.6 5.8 L/min and the volume of distribution was 205 170 L. 

Metabolism/Excretion - About 50% is excreted in the urine as the unchanged drug and 30% as metabolites (20% mono-N-dealkyIdisopyramide [MND]). The plasma concentration of MND is approximately one-tenth that of disopyramide. The mean plasma half-life is 6.7 hours (range, 4 to 10 hours). In impaired renal function, half-life values ranged from 8 to 18 hours. Therefore, decrease the dose in renal failure to avoid drug accumulation. 

In healthy subjects, the elimination half-life is 10 to 12 hours. Hepatic impairment prolongs it to a mean of 25 hours. Little change in half-life occurs with reduced renal function. In eight patients with creatinine clearance less than 10 mL/min, the mean plasma elimination half-life was 15.7 hours in... 

Pharmacology Bretylium tosylate inhibits norepinephrine release by depressing adrenergic nerve terminal excitability, inducing a chemical sympathectomy-like state. Bretylium blocks the release of norepinephrine in response to neuron stimulation. Peripheral adrenergic blockade causes orthostatic hypotension but has less effect on supine blood pressure. It has a positive inotropic effect on the myocardium. Pharmacokinetics Peak plasma concentration and peak hypotensive effects are seen within 1 hour of IM administration. However, suppression of premature ventricular beats is not maximal until 6 to 9 hours after dosing, when mean plasma concentration declines to less than 50% of peak level. Antifibrillatory effects occur within minutes of an IV injection. Suppression of ventricular tachycardia and other ventricular arrhythmias develops more slowly, usually 20 minutes to 2 hours after parenteral administration. 

Excretion - Following discontinuation of chronic oral therapy, amiodarone has a biphasic elimination with an initial one-half reduction of plasma levels after 2.5 to 107 days. A much slower terminal plasma elimination phase shows a half-life of the parent compound of approximately 53 days. For the metabolite, mean plasma elimination half-life was approximately 61 days. Antiarrhythmic effects persist for weeks or months after the drug is discontinued. 

Renal function impairment The pharmacokinetics of diltiazem and verapamil in patients with impaired renal function are similar to the pharmacokinetic profile of patients with normal renal function. However, caution is still advised. Nifedipine s plasma concentration is slightly increased in patients with renal impairment. Nicardipine s mean plasma concentrations, AUC and maximum concentration were about 2-fold higher in patients with mild renal impairment. 

The mean plasma half-life ranged from 2.7 to 5.5 hours in healthy young adults. 

Excretion - The mean plasma elimination half-life of dexmethylphenidate is approximately 2.2 hours. 

MefaboZ/sm/Excref/on- Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose). The mean plasma elimination half-life is 21 hours after single or multiple doses. Overall, plasma clearance is approximately 20 to 30 mL/min following oral administration. 

Mefabo//s/T - The observed plasma half-life for IV sulfasalazine is 7.6 hours. The primary route of metabolism of SP is via acetylation to form AcSP. The rate of metabolism of SP to AcSP is dependent on acetylator phenotype. In fast acetylators, the mean plasma half-life of SP is 10.4 hours, while in slow acetylators it is 14.8 hours. 

Excretion - Ertapenem is eliminated primarily by the kidneys. The mean plasma half-life in healthy young adults is approximately 4 hours, and the plasma clearance is approximately 1.8 L/hour. 

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