Injection Site Residues and Flip-Flop Pharmacokinetics

1 Injection Site Residues and Flip-Flop Pharmacokinetics 

However, for many AMDs and indeed drugs of other classes (e.g., anthelmintics), there has long been a practice of developing slow-release (depot) formulations, administered intramuscularly, subcutaneously, or as pour-on products, for use in farm animal species. As discussed in Section 2.2.3, these products commonly display flip-flop pharmacokinetics, in which the terminal half-life represents a slow absorption phase and is longer than the elimination half-life determined after intravenous dosing. The advantages and disadvantages of depot preparations are summarized in Table 2.15. 

The potential complexity of the pharmacokinetic profile for slow-release products is illustrated by the early study of Toutain and Raynaud. These workers administered a 20% w/v solution of oxytetracycline intramuscularly to young calves at a dose rate of 20 mg/kg. The data best fitted an open two-compartment model (central and peripheral) with two absorption compartments (rapid and slow release). The rapid absorption phase was attributed to immediate 

TABLE 2.15 Advantages and Disadvantages of Parenteral Depot Formnlations of AMDs 

Provide products with long duration of action, requiring single dosing and/or or a long (48-72-h) dosing interval 

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