Time to peak

Time to peak plasma concentration depends on the rate of IV dosing but is usually achieved in 45—90 seconds. Therapeutic plasma concentrations are 1.5—5.0 )J.g/mL, and concentrations above 5 )J.g/mL maybe toxic. The elimination half-life after a bolus iv dose is 8 min the elimination half-life after a 24 h iv infusion is about 100 min. The dmg is eliminated by the kidneys. Ten percent is unchanged and the remainder is in the form of inactive metabolites... 

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

The proteetion level of an arrester, is a function of the magnitude of arrester discharge current (/ ), and the time to peak of the surge (/ ). and is influenced by the following. 

Inhibition of the Na+/K+-ATPase leads to a loss of potassium and an increase of sodium within the cell. Secondary intracellular calcium is increased via the Na VCa -exchanger. This results in a positive inotropic effect in the myocardium, with an increase of peak force and a decrease in time to peak tension. Besides this, cardiac glycosides increase vagal activity by effects on the central vagal nuclei, the nodose ganglion and increase in sensitivity of the sinus node to acetylcholine. 

Photo flash Compositions. Workers at PicArsn have investigated a series of mixts of K perchlorate with powd metals for use as photoflash compns. Info on candlepower, time to peak luminosity, and duration of flash, as well as performance at sea level and 1 x 10s feet, are given for each compn (Ref 23). A standard mil photo flash compn is given as 40% atomized Al, 30% Ba nitrate, and 30% K perchlorate (Ref 22, P 274)... 

It should be noted that, in two of these studies, " the perfusion parameter used to define the mismatch was not CBF or MTT, but instead the time it took for contrast concentration to reach peak concentration in each image voxel after contrast injection ( time to peak or TTP). TTP measurements are often used as rough approximations of MTT measurements because calculation of CBF and MTT are somewhat complex, requiring a mathematical process called deconvolution. The details of deconvolution are beyond the scope of this chapter, and the reader is referred to other sources for further explanation. In many clinical settings, maps of parameters like TTP that do not require deconvolution may be available much more quickly than those that do require deconvolution. TTP is less specific than MTT in detecting underperfused tissue because it does not distinguish between delayed contrast arrival time (such as that related to perfusion via collateral vessels) and truly prolonged intravascular transit time. 

Drug Name Time to Peak Half-Life Approved Dose... 

Sub-type inhibition of the 5a-reductase enzyme Percent of inhibition of serum dihydrotestosterone level Percent of patients with reduction in serum dihyrotestosterone Time to peak onset of reduction in serum dihydrotestosterone level Percent inhibition of intraprostatic d i hy d rotestosterone Half-life... 

Pharmacodynamics Duration 1-4 weeks Absorption IM slow Time to peak serum levels 12-24 hours Duration 15-24 hours Absorption IM slow Distribution Poor blood-brain barrier penetration, enters breast milk Metabolism =30% hepatic inactivation Protein binding 65% Time to peak serum levels 1-4 hours Excretion Urine (60-90% as unchanged drug) Clearance Renal... 

Mercaptopurine (6-MP) is an oral purine analog that is converted to a ribonucleotide to inhibit purine synthesis. Mercaptopurine is converted into thiopurine nucleotides, which are catabolized by thiopurine S-methyltransferase (TPMT), which is subject to genetic polymorphisms and may cause severe myelosuppression. TPMT status may be assessed prior to therapy to reduce drug-induced morbidity and the costs of hospitalizations for neutropenic events. Mercaptopurine is poorly absorbed, with a time to peak concentration of 1 to 2 hours after an oral dose. The half-life is 21 minutes in pediatric patients and 47 minutes in adults. Mercaptopurine is used in the treatment of acute lymphocytic leukemia and chronic myelogenous leukemia. Significant side effects include myelosuppression, mild nausea, skin rash, and cholestasis. When allopurinol is used in combination with 6-MP, the dose of 6-MP must be reduced by 66% to 75% of the usual dose because allopurinol blocks the metabolism of 6-MP. 

Hydroxyurea is an oral drug that inhibits ribonucleotide reductase, which converts ribonucleotides into the deoxyribuon-cleotides used in DNA synthesis and repair. The time to peak concentrations of hydroxyurea is 1 to 2 hours after oral administration. Approximately 50% is degraded by the liver to form urea and respiratory carbon dioxide. The remainder is excreted by the kidney. The half-life ranges from 3.5 to 4.5 hours. Hydroxyurea has shown clinical activity in the treatment of chronic myelocytic leukemia, polycythemia vera, and thrombocytosis. The major side effects are myelo-suppression, nausea and vomiting, diarrhea, and constipation. Rash, mucositis, and renal tubular dysfunction occur rarely. 

Tretinoin, also referred to ATRA, which stands for all-trans-retinoic acid, is a retinoic acid that is not cytotoxic but promotes the maturation of early promyelocytic cells and is specific to the t(15 17) cytogenetic marker. The time to peak concentrations is 1 to 2 hours after an oral dose. The elimination half-life is 21 to 51 minutes.32 These maroon-and-gold capsules are dosed at 45 mg/m2 per day divided into two doses. The most significant side effect is the retinoic acid syndrome, which may occur anywhere from the first couple of days of therapy until the end of therapy and consists of symptoms of... 

Erlotinib, whose pharmacology is not entirely understood, is believed to inhibit the intracellular phosphorylation of the epidermal growth factor receptor. Erlotonib is about 60% absorbed after oral administration food increases bioavailability to almost 100%. The time to peak concentrations is... 

Sorafenib is a multikinase inhibitor that inhibits both intracellular and extracellular kinases to decrease renal cell cancer proliferation. The half-life of sorafenib is 25 to 48 hours, with a bioavailability of 38% to 49% and a time to peak concentration of 3 hours. Sorafenib is metabolized primarily by the liver by CYP450 3A4. Sorafenib is used for the treatment of renal cell cancer. The primary side effects of sorafenib include rash, hand-foot skin reaction, diarrhea, pruritus, and elevations in serum lipase. 

Identical doses of a capsule preparation (X) and a tablet preparation (Y) of the same drug were compared on a blood concentration-time plot with respect to peak concentration, time to peak concentration, and AUC after oral administration as shown in the figure below This comparison was made to determine which of the following ... 

The answer is e. (Hardman, p 21J The fraction of a drug dose absorbed after oral administration is affected by a wide variety of factors that can strongly influence the peak blood levels and the time to peak blood concentration. The Vd and the total body clearance (Vd x first-order fte) also are important in determining the amount of drug that reaches the target tissue. Only the area under the blood concentration-time curve, however, reflects absorption, distribution, metabolism, and excretion factors it is the most reliable and popular method of evaluating bioavailability... 

Time to Peak Plasma Level Generic Name (hours)... 

Although the time to peak drug concentration is often on the order of 1 to 2 h, depot preparations given by IM injection are absorbed extremely slowly. Numerous... 

Pharmacokinetic concentration-time curves for a drug and ifs mefabolifes are used to identify primary exposure metrics such as AUC, or which are not time-dependent unlike the sequential measurements of concentration over time. A peak plasma concentration of a drug is often associated with a PD response, especially with an adverse event. There can be large inter-individual variability in the time-to-peak concentration, and closely spaced sampling times are often critical to determining the peak plasma concentration accurately in individual patients because of differences in demographics, disease states, and food effects, if any. All these elements are clearly spelled out in the protocols written to conduct these studies. 

Nicotine nasal spray is marketed as a pharmacy-only medication in the UK, and is available only by prescription in the USA. The nasal spray was designed to deliver doses of nicotine to the smoker more rapidly than other NRT products. The device is a multidose bottle with a pump that delivers 0.5 mg of nicotine per 50-pL squirt. Each dose consists of two squirts, one to each nostril. Nicotine from the nasal spray is absorbed into the blood more rapidly than from the gum (Schneider et al. 1996). Venous plasma concentrations after a single 1-mg dose range between 5 and 12 ng mL Time to peak plasma concentration (7j ax) with nasal administration is around 11-13 min for 1-mg doses. This rise time is slower than for cigarette delivery (Henningfield et al. 1993), but faster than for the other NRT products. 

Metabolism - Following an oral dose of dipyridamole, the average time to peak concentration is approximately 75 minutes. The decline in plasma concentration fits a two-compartment model. The half-life (the initial decline following peak concentration) is approximately 40 minutes. The half-life (the terminal decline in plasma concentration) is approximately 10 hours. Dipyridamole is highly bound to plasma proteins. It is metabolized in the liver where it is conjugated as a glucuronide and excreted with the bile. 

Absorption - Following administration of a single 0.5 mg dose of a soft gelatin capsule, time to peak serum concentrations (T ax) dutasteride occurs within... 

Food effect Delays time to peak concentration does not alter extent of absorption 28% decrease in C ax > 1 delay in T ax ( I h) no overall change in AUC... 

Absorption - ZWeuton is rapidly absorbed upon oral administration with a mean time to peak plasma concentration (T ax) I hours and a mean peak level (Cmax) of 4.98 mcg/mL. Plasma concentrations of zileuton are proportional to... 

Drug/Food interactions Administration of tolmetin with milk decreased total tolmetin bioavailability by 16%. When tolmetin was taken immediately after a meal, peak plasma concentrations were reduced by 50%, while total bioavailability was again decreased by 16%. Peak concentration of etodolac is reduced by about 50% and the time to peak is increased by 1.4 to 3.8 hours following administration with food however, the extent of absorption is not affected. Food may reduce the rate of absorption of oxaprozin, but the extent is unchanged. 

Maprotiline-The mean time to peak is 12 hours. The elimination half-life averages 43 hours. Binding to serum proteins is approximately 88%. 

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