Intravenous single dose

Lund, J., Thayssen, P., Mengel, H., Pedersen, O.L., Kristensen, C.B., and Gram L.F. (1982) Paroxetine pharmacokinetics and cardiovascular effects after oral and intravenous single doses in man. Acta Pharmacol Toxicol (Copenh) 51 351—357. 

Lung Dog Pulmonary oedema 100 mg/kg intravenous Single dose Graham (1965)... 

Commercially available containers for use with parenteral products include single-dose ampuls that are heat sealed and opened by snapping at the point of least diameter, vials for multidose use, and botdes and pHable bags that are used for large volumes such as needed in intravenous infusions. Container size can vary from 1 mL to 1 L. Generally volumes up to 100 mL are available as ampuls or vials. 

Tenecteplase (TNKase) is the first thrombolytic drug that can be administered during a period of 5 seconds in a single dose The drug is administered intravenously only and offers the fastest administration of a thrombolytic in the treatment of an acute MI. Specific instructions for reconstitution come with the drug. The drug is reconstituted immediately before use because it contains no antibacterial preservatives. 

Most injections are formulated as aqueous solutions, with Water for Injections BP as the vehicle. The formulation of injections depends upon several factors, namely the aqueous solubility of the active ingredient, the dose to be employed, thermal stability of the solution, the route of injection and whether the product is to be prepared as a multidose one (i.e. with a dose or doses removed on different occasions) or in a singledose form (as the term suggests, only one dose is contained in the injection). Nowadays, most injections are prepared as single-dose forms and this is mandatory for certain routes, e.g. spinal injections such as the intrathecal route and large-volume intravenous infusions (section 2.2). Multidose injections may require the inclusion of a suitable... 

Fig. 39.4. (a) One-compartment open model with single-dose intravenous injection of a dose D. The transfer constant of elimination (excretion and metabolism) is kp - (b) Time course of the plasma concentration Cp and of the contents in the elimination pool Xp. 

The effect of incomplete absorption is that only a fraction of a single-dose D is made available to the central plasma compartment. The solution of the previous model needs, therefore, to be modified by replacing the term D by F D. Consequently the area under the curve AUCg under incomplete extravascular absorption will be smaller than the maximal AUC that results from complete absorption. The latter, as we have seen is equal to the AUC obtained from a single intravenous injection, which we denote by AUC,. These considerations can be summarized as follows ... 

In the previous discussion of the one- and two-compartment models we have loaded the system with a single-dose D at time zero, and subsequently we observed its transient response until a steady state was reached. It has been shown that an analysis of the response in the central plasma compartment allows to estimate the transfer constants of the system. Once the transfer constants have been established, it is possible to study the behaviour of the model with different types of input functions. The case when the input is delivered at a constant rate during a certain time interval is of special importance. It applies when a drug is delivered by continuous intravenous infusion. We assume that an amount Z) of a drug is delivered during the time of infusion x at a constant rate (Fig. 39.10). The first part of the mass balance differential equation for this one-compartment open system, for times t between 0 and x, is given by ... 

Usually, one has obtained an estimate for the elimination constant and the distribution volume Vp from a single intravenous injection. These pharmacokinetic parameters, together with the interval between administrations 0 and the single-dose D, then allow us to compute the steady-state peak and trough values. The criterion for an optimal dose regimen depends on the minimum therapeutic concentration (which must be exceeded by and on the maximum safe... 

In the case of a one-compartment open model with single-dose intravenous administration, the mean residence time is simply the inverse of the elimination transfer constant kp, since according to the above definition we obtain ... 

When a single-dose intravenous and an oral (or other extravascular) plasma curve are both available from the same subject(s) one can define the mean absorption time MAT by means of the mean residence time obtained from the intravenous curve MRT, and the extravascular curve MRT ... 

Ondansetron (Zofran) 32 mg intravenously prior to chemotherapy as a single dose, or 0.1 5 mg/kg prior to chemotherapy, repeat at 4 and 8 hours or 8 mg orally 30 minutes prior to chemotherapy, repeat at 4 and 8 hours and every 12 hours for 1 -2 days after chemotherapy completion ... 

Dose 1 5 mg/kg per day (1 g) and 1 0 mg/kg in persons older than 50 years of age (750 mg). Usual dose 750-1 000 mg administered intramuscularly or intravenously, given as a single dose 5-7 days/week, and reduced to two or three times per week after the first 2 4 months or after culture conversion, depending on the efficacy of the other drugs in the regimen. 

Ceftriaxone 25 to 50 mg/kg intravenously or intramuscularly as a single dose for ophthalmia neonatorum or infants born to mothers with gonococcal infection as prophylaxis... 

Guinea pig, neonate— adult 241 Am citrate aqueous solution, single dose applied to tongue, 0.6-0.9 pig/kg % 1.1 0.55 0.19 0.17 0.06 0.03 0.02 0.005 Age 0.5 d 1 d 5 d 10 d 15 d 20 d 30 d adult Absorption estimate based on comparisons with liver and carcass 241 Am after an intraperitoneal dose (neonates) or intravenous dose (adults), with adjustment for excretion Bomford and Harrison 1986... 

Mihaly et al. [127] examined the pharmacokinetics of primaquine in healthy volunteers who received single oral doses of 15, 30, and 45 mg of the drug, on separate occasions. Each subject received an intravenous tracer dose of 14C-prima-quine (7.5 pCi), simultaneously with 45 mg oral dose. Absorption of primaquine was virtually complete with a mean absorption bioavailability of 0.96. Elimination half-life, oral clearance, and apparent volume of distribution for both primaquine and the carboxylic acid metabolite were unaffected by either dose size or route of administration. 

The single-dose toxicity studies were performed in two mammalian species, rat and mouse, by the route used in clinical practice, that is oral, as well as that ensuring adequate systemic exposure to the drug, that is intravenous. The subacute (3 months) toxicity studies were correctly carried out in the two animal species (rat, dog) in which also the pharmacokinetics was studied. Since in accordance with the International Conference on Harmonization (CPMP/ICH/286/95), 3-month toxicity studies support clinical trials for up to 1 month s duration (the longest duration of drug administration in clinical use), chronic toxicity studies have not been performed. 

There are many circumstances when a single-dose intravenous (IV) study can provide useful information for example, if the intended treatment route is intraper-itoneal (i.p.), or if the product will be administered to an open wound or injected into a muscle or a tumor, it might accidentally enter a blood vessel, and the knowledge gained from an IV study would be of value as well as one by the clinical route. Hence, if the intended clinical route is not IV, the absence of an additional study with IV dosing would require specific justification. 

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