In vivo pharmacokinetic studies (parenteral administration)
If you would like to:
find a route that avoids side effects for a compound you are discovering,
evaluate repositioning by changing the dosage form, from both pharmacokinetic and efficacy perspectives , or
discover an optimal compound that suits the route you targeted,
It is important to compare a variety of routes and select an appropriate experimental animal species for optimal dosing design.
Axcelead DDP will utilize our considerable accumulated experience and technological capabilities to propose an optimal route of administration that suits your needs and modalities.
Feature 2 Multilateral evaluation from pharmacokinetics, efficacy, and safety points of view
onsideration of the balance among pharmacokinetics, efficacy and safety as well as the results of pharmacokinetic studies is required. Axcelead DDP will provide one-stop speedy support for these diversified evaluations and analyses because it has all of the required functions necessary for drug discovery research.
For some routes of administration, Axcelead DDP can provide services ranging from judgement of appropriateness of compounds to human prediction.
Feature 3 Ability to deal with the next-generation transdermal delivery system
We team up with PassPort Technologies, Inc., San Diego, USA, to deal with studies using the novel active transdermal delivery technology, PassPort System®.
We will explore new possibilities for routes of administration.
◆ Details of routes of administration
■ Nasal administration
- Administration of drug liquid to the animal’s nasal cavity under conscious conditions (for rats) or under anesthesia.
- This type of administration is useful for drugs that are expected to act immediately, will be greatly affected by the first-pass effect, or can be easily inactivated in the gastrointestinal tract, because capillaries are densely distributed in nasal mucosa.
- The method is suitable for central nervous system diseases, because drugs can be delivered from nasal mucosa to the brain without passing through the blood-brain barrier.
■ Pulmonary administration
- Administration of drug powder or liquid to the animal’s lungs by spraying it under anesthesia.
- In addition to direct exposure to the lungs or the bronchi, absorption of drugs with low membrane permeability into circulating blood can be expected due to the large surface area of the lung, with densely distributed capillaries.
■ Sublingual administration
- Administration of drug liquid to the animal’s sublingual space under conscious conditions (for monkeys) or under anesthesia.
- Immediate action can be expected because drugs will be rapidly absorbed from oral mucosa.
▶▶▶Example of parenteral administration
lasma concentrations after intravenous, pulmonary, nasal, and sublingual administration of desmopressin to cynomolgus monkeys. The optimal route of administration suitable for drug characteristics will be explored on the basis of concentration-time profiles after administration.
■ Transdermal administration
- Administration by applying drug liquid on, or adhering patch formulation to, the animal’s skin.
- Persistent effects can be expected because the drugs will be gradually absorbed through the skin.
■ Next-generation transdermal delivery system (PassPort Technologies, Inc.)
- he electric current flows instantly through a metal filament pressed against the skin to produce heat. The thermal energy vaporizes the stratum corneum and makes hundreds of 20- to 50-μm micropores, and then a patch formulation is attached for administration. No pain will be felt because no needles are used and heat is applied to very shallow regions. The efficacy and safety of the system have already been demonstrated in clinical studies involving at least 5000 subjects.
Absorption of small molecules with low membrane permeability, which are difficult to be absorbed by transdermal administration, or middle and large molecules such as peptides, nucleic acids, proteins, and antibodies were dramatically improved, and some cases realized a concentration in circulating blood comparable to that of subcutaneous administration.
- The number and depth of micropores are adjustable depending on how the filament is designed. Adding excipients to the patch formulation allows the absorption rate to be controlled.
- Improved drug administration compliance can also be expected by introducing the Internet of Things.
◆ Our experience in pharmacokinetic studies using various animal species
We will also provide support for intraperitoneal, intramuscular, intraduodenal, intrarectal, and other administrations. Please consult with us.